Nutrient chapter

Niacin (vitamin B3)

Vitamin B3 nutritional family, including nicotinic acid and nicotinamide. Precursor forms, NAD+/NADH and NADP+/NADPH have separate identities; chemical form and experimental exposure determine each claim.

116 recorded mechanisms · 13 availability situations · 10 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.

Human KMO membrane assays measured kynurenine conversion to 3-hydroxykynurenine with NADPH; at 200 micromolar NADPH, kynurenine Km was 2 micromolar.
Human kynurenine 3-monooxygenase / KMO → L-Kynurenine source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B2-FAD and nicotinamide-containing NADPH support a branch upstream of de novo niacin synthesis.
evidence_location
Fig 2f and Methods: kinetic assays; interpret species separately
experimental_model
Human KMO in Sf9 membrane preparations; mass-spectrometry kinetics; separate P. fluorescens KMO crystallography.
exposure
Purified-enzyme assay
limitations
Human functional assays and bacterial structures are distinct evidence; this experiment did not test dietary B2 restriction or total NAD synthesis.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
A flavin enzyme directs tryptophan-derived kynurenine into the hydroxylated branch.
primary_references
[hutchinson2017] Structural and mechanistic basis of differentiated inhibitors of the acute pancreatitis target kynurenine-3-monooxygenase. (2017). https://pubmed.ncbi.nlm.nih.gov/28604669/ DOI: 10.1038/ncomms15827
tissue_or_cell_type
Sf9 membrane fraction expressing human KMO
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1234–1246
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human KMO in Sf9 membrane preparations; mass-spectrometry kinetics; separate P. fluorescens KMO crystallography. · source_derived_draft · unverified_draft
### b2-kmo-kynurenine-hydroxylation Human KMO membrane assays measured kynurenine conversion to 3-hydroxykynurenine with NADPH; at 200 micromolar NADPH, kynurenine Km was 2 micromolar. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A flavin enzyme directs tryptophan-derived kynurenine into the hydroxylated branch. organism: Homo sapiens tissue_or_cell_type: Sf9 membrane fraction expressing human KMO experimental_model: Human KMO in Sf9 membrane preparations; mass-spectrometry kinetics; separate P. fluorescens KMO crystallography. limitations: Human functional assays and bacterial structures are distinct evidence; this experiment did not test dietary B2 restriction or total NAD synthesis. exposure: Purified-enzyme assay cross_nutrient: B2-FAD and nicotinamide-containing NADPH support a branch upstream of de novo niacin synthesis. evidence_location: Fig 2f and Methods: kinetic assays; interpret species separately [hutchinson2017] Structural and mechanistic basis of differentiated inhibitors of the acute pancreatitis target kynurenine-3-monooxygenase. (2017). https://pubmed.ncbi.nlm.nih.gov/28604669/ DOI: 10.1038/ncomms15827
Complete structured claim and evidence
Kmo knockout reduced quinolinate to about 3% of wild-type liver content but about 80% of wild-type brain content.
Mouse kynurenine 3-monooxygenase / Kmo → Quinolinic acid source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
A B2-dependent step feeds the tryptophan-to-niacin pathway with tissue-specific dependence.
evidence_location
Results: liver Fig 4 and brain Fig 7; matching abstract conclusion
experimental_model
Constitutive Kmo knockout and wild-type mice, approximately two months old; liver and brain metabolite assays.
exposure
Constitutive Kmo deletion
limitations
Genetic deletion; alternative routes were proposed but not all directly traced.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Mus musculus
plain_language
Removing this enzyme affected downstream metabolites differently across tissues.
primary_references
[giorgini2013] Targeted deletion of kynurenine 3-monooxygenase in mice: a new tool for studying kynurenine pathway metabolism in periphery and brain. (2013). https://pubmed.ncbi.nlm.nih.gov/24189070/ DOI: 10.1074/jbc.m113.503813
tissue_or_cell_type
Liver and brain
trigger_kind
machinery_impairment Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1248–1260
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Constitutive Kmo knockout and wild-type mice, approximately two months old; liver and brain metabolite assays. · source_derived_draft · unverified_draft
### b2-kmo-loss-quinolinate-tissue Kmo knockout reduced quinolinate to about 3% of wild-type liver content but about 80% of wild-type brain content. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Removing this enzyme affected downstream metabolites differently across tissues. organism: Mus musculus tissue_or_cell_type: Liver and brain experimental_model: Constitutive Kmo knockout and wild-type mice, approximately two months old; liver and brain metabolite assays. limitations: Genetic deletion; alternative routes were proposed but not all directly traced. exposure: Constitutive Kmo deletion cross_nutrient: A B2-dependent step feeds the tryptophan-to-niacin pathway with tissue-specific dependence. evidence_location: Results: liver Fig 4 and brain Fig 7; matching abstract conclusion [giorgini2013] Targeted deletion of kynurenine 3-monooxygenase in mice: a new tool for studying kynurenine pathway metabolism in periphery and brain. (2013). https://pubmed.ncbi.nlm.nih.gov/24189070/ DOI: 10.1074/jbc.m113.503813
Complete structured claim and evidence
Measured liver and brain NAD+ contents were not significantly different between Kmo-knockout and wild-type mice.
Mouse kynurenine 3-monooxygenase / Kmo → NAD+ source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Bounds the B2-KMO-niacin link: a cofactor-dependent pathway step is not proof that total NAD pools must fall.
evidence_location
Results: liver Fig 4 and brain Fig 7; matching abstract conclusion
experimental_model
Constitutive Kmo knockout and wild-type mice, approximately two months old; liver and brain metabolite assays.
exposure
Constitutive Kmo deletion
limitations
Steady-state pools do not measure de novo synthesis flux; diet and salvage can affect the result.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Mus musculus
plain_language
Losing the KMO branch did not collapse the measured NAD+ pools.
primary_references
[giorgini2013] Targeted deletion of kynurenine 3-monooxygenase in mice: a new tool for studying kynurenine pathway metabolism in periphery and brain. (2013). https://pubmed.ncbi.nlm.nih.gov/24189070/ DOI: 10.1074/jbc.m113.503813
tissue_or_cell_type
Liver and brain
trigger_kind
machinery_impairment Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1262–1274
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Constitutive Kmo knockout and wild-type mice, approximately two months old; liver and brain metabolite assays. · source_derived_draft · unverified_draft
### b2-kmo-loss-nad-preserved Measured liver and brain NAD+ contents were not significantly different between Kmo-knockout and wild-type mice. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Losing the KMO branch did not collapse the measured NAD+ pools. organism: Mus musculus tissue_or_cell_type: Liver and brain experimental_model: Constitutive Kmo knockout and wild-type mice, approximately two months old; liver and brain metabolite assays. limitations: Steady-state pools do not measure de novo synthesis flux; diet and salvage can affect the result. exposure: Constitutive Kmo deletion cross_nutrient: Bounds the B2-KMO-niacin link: a cofactor-dependent pathway step is not proof that total NAD pools must fall. evidence_location: Results: liver Fig 4 and brain Fig 7; matching abstract conclusion [giorgini2013] Targeted deletion of kynurenine 3-monooxygenase in mice: a new tool for studying kynurenine pathway metabolism in periphery and brain. (2013). https://pubmed.ncbi.nlm.nih.gov/24189070/ DOI: 10.1074/jbc.m113.503813
Complete structured claim and evidence
Riboflavin-deficient baboons excreted approximately one tenth as much urinary 3-hydroxykynurenine in the reported dietary comparison.
Riboflavin (vitamin B2) → 3-Hydroxy-L-kynurenine source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Dietary B2 status influences a tryptophan/niacin-pathway readout.
evidence_location
Abstract
experimental_model
Dietary riboflavin-deficient, pyridoxine-deficient, pair-fed and natural-diet baboons; urinary and erythrocyte measurements.
exposure
Experimental riboflavin-deficient diet
limitations
Indexed abstract does not give diet duration or group size; urinary output is not a direct tissue KMO flux measurement.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Papio species (baboon)
plain_language
Dietary B2 deficiency changed a measured tryptophan-pathway product.
primary_references
[verjee1975] Tryptophan metabolism in baboons: effect of riboflavin and pyridoxine deficiency. (1975). https://pubmed.ncbi.nlm.nih.gov/23659/
tissue_or_cell_type
Urine
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1276–1288
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dietary riboflavin-deficient, pyridoxine-deficient, pair-fed and natural-diet baboons; urinary and erythrocyte measurements. · source_derived_draft · unverified_draft
### b2-baboon-urinary-hydroxykynurenine Riboflavin-deficient baboons excreted approximately one tenth as much urinary 3-hydroxykynurenine in the reported dietary comparison. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Dietary B2 deficiency changed a measured tryptophan-pathway product. organism: Papio species (baboon) tissue_or_cell_type: Urine experimental_model: Dietary riboflavin-deficient, pyridoxine-deficient, pair-fed and natural-diet baboons; urinary and erythrocyte measurements. limitations: Indexed abstract does not give diet duration or group size; urinary output is not a direct tissue KMO flux measurement. exposure: Experimental riboflavin-deficient diet cross_nutrient: Dietary B2 status influences a tryptophan/niacin-pathway readout. evidence_location: Abstract [verjee1975] Tryptophan metabolism in baboons: effect of riboflavin and pyridoxine deficiency. (1975). https://pubmed.ncbi.nlm.nih.gov/23659/
Complete structured claim and evidence
Human kynureninase crystallography resolves the PLP-containing active-site architecture.
PLP → Human kynureninase / KYNU source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B6-dependent KYNU acts in the pathway leading from tryptophan toward niacin/NAD precursors.
experimental_model
Recombinant human KYNU crystallography and biochemical characterization
limitations
Purified-enzyme evidence does not define dietary requirements or cellular PLP thresholds.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
KYNU uses active B6 in the tryptophan pathway.
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 873–883
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-plp Human kynureninase crystallography resolves the PLP-containing active-site architecture. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: KYNU uses active B6 in the tryptophan pathway. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Recombinant human KYNU crystallography and biochemical characterization limitations: Purified-enzyme evidence does not define dietary requirements or cellular PLP thresholds. cross_nutrient: B6-dependent KYNU acts in the pathway leading from tryptophan toward niacin/NAD precursors. [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
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
Under niacin-free feeding, B6-free rats had lower apparent tryptophan-to-niacin conversion than rats receiving B6.
Vitamin B6 → Apparent tryptophan-to-niacin conversion from urinary metabolites source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Dietary B6 status affected apparent tryptophan-to-niacin conversion.
experimental_model
Young male Wistar rats; four controlled diets for 19 days
exposure
Young male Wistar rats; 19-day diets; conversion contrast within niacin-free groups
limitations
Apparent urinary conversion, not net synthesis or a human requirement.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Rattus norvegicus
plain_language
B6 shortage reduced this dietary study's estimate of niacin production from tryptophan.
primary_references
[b6-niacin-1995] Effects of Vitamin B6 Deficiency on the Conversion Ratio of Tryptophan to Niacin (1995). https://doi.org/10.1271/bbb.59.2060 DOI: 10.1271/bbb.59.2060
tissue_or_cell_type
Whole-animal dietary intake and urine
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 898–909
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Young male Wistar rats; four controlled diets for 19 days · source_derived_draft · unverified_draft
### b6-met-rat-niacin-conversion Under niacin-free feeding, B6-free rats had lower apparent tryptophan-to-niacin conversion than rats receiving B6. Condition category: nutrient_deficiency nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: B6 shortage reduced this dietary study's estimate of niacin production from tryptophan. organism: Rattus norvegicus tissue_or_cell_type: Whole-animal dietary intake and urine experimental_model: Young male Wistar rats; four controlled diets for 19 days limitations: Apparent urinary conversion, not net synthesis or a human requirement. cross_nutrient: Dietary B6 status affected apparent tryptophan-to-niacin conversion. exposure: Young male Wistar rats; 19-day diets; conversion contrast within niacin-free groups [b6-niacin-1995] Effects of Vitamin B6 Deficiency on the Conversion Ratio of Tryptophan to Niacin (1995). https://doi.org/10.1271/bbb.59.2060 DOI: 10.1271/bbb.59.2060
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
SELENOO can split NAD into two smaller molecules.
SELENOO catalyzes NAD+ hydrolysis to NMN and AMP.
SELENOO → NAD+ source_derived_draftliterature_reviewed:direct_experimental
Experimental context and source evidence
cell_type
experimental cells
experimental_model
Biochemical and cellular assays
limitations
Recent 2026 finding; no dietary-dose inference.
organism
mammalian
Selenium: literature corrections and mechanism additions · lines 438–448
Metabolic Ledger literature curation, 17 September 2026; primary papers linked individually · supports · Biochemical and cellular assays · secondary_verified · secondary_verified
## selenoo-hydrolyzes-nad SELENOO can split NAD into two smaller molecules. SELENOO catalyzes NAD+ hydrolysis to NMN and AMP. Organism: mammalian Cell type: experimental cells Experimental model: Biochemical and cellular assays Limitations: Recent 2026 finding; no dietary-dose inference. Primary reference: [NAD+ hydrolysis catalyzed by SelO is required for mitochondrial homeostasis](https://pubmed.ncbi.nlm.nih.gov/41806834/)
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
GSR reduces one glutathione-disulfide molecule to two reduced glutathione molecules using the NADPH/FAD catalytic relay.
Glutathione reductase / GSR → GSSG source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B2-FAD supports GSH recycling; selenium-dependent GPX use of GSH is a separate reaction.
evidence_location
Results: NADPH binding; Fig 1 consensus cycle; GSH/GSSG complexes
experimental_model
Purified human glutathione reductase crystals with natural substrates, 0.95-1.1-A resolution, chemically reduced controls.
exposure
Purified-enzyme assay
limitations
GSR is not glutathione peroxidase; this record does not show that B2 improves selenium repletion.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
This enzyme recycles glutathione after oxidation.
primary_references
[berkholz2008] Catalytic cycle of human glutathione reductase near 1 A resolution. (2008). https://pubmed.ncbi.nlm.nih.gov/18638483/ DOI: 10.1016/j.jmb.2008.06.083
tissue_or_cell_type
Purified human GSR
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1332–1344
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human glutathione reductase crystals with natural substrates, 0.95-1.1-A resolution, chemically reduced controls. · source_derived_draft · unverified_draft
### b2-gsr-gssg-to-gsh GSR reduces one glutathione-disulfide molecule to two reduced glutathione molecules using the NADPH/FAD catalytic relay. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: This enzyme recycles glutathione after oxidation. organism: Homo sapiens tissue_or_cell_type: Purified human GSR experimental_model: Purified human glutathione reductase crystals with natural substrates, 0.95-1.1-A resolution, chemically reduced controls. limitations: GSR is not glutathione peroxidase; this record does not show that B2 improves selenium repletion. exposure: Purified-enzyme assay cross_nutrient: B2-FAD supports GSH recycling; selenium-dependent GPX use of GSH is a separate reaction. evidence_location: Results: NADPH binding; Fig 1 consensus cycle; GSH/GSSG complexes [berkholz2008] Catalytic cycle of human glutathione reductase near 1 A resolution. (2008). https://pubmed.ncbi.nlm.nih.gov/18638483/ DOI: 10.1016/j.jmb.2008.06.083
Complete structured claim and evidence
Purified full-length human MTHFR had apparent Km values of 35.5 micromolar for NADPH and 3760 micromolar for NADH.
Methylenetetrahydrofolate reductase / MTHFR → NADPH source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Folate reduction uses nicotinamide reducing equivalents.
experimental_model
Recombinant human MTHFR; kinetics and structures.
limitations
Affinity does not quantify cellular flux.
nutrient_topic
Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. · Folate (vitamin B9)
organism
Homo sapiens
plain_language
MTHFR strongly preferred NADPH in this assay.
primary_references
[froese-2018] Structural basis for the regulation of human 5,10-methylenetetrahydrofolate reductase by phosphorylation and S-adenosylmethionine inhibition (2018). https://pubmed.ncbi.nlm.nih.gov/29891918/ DOI: 10.1038/s41467-018-04735-2
tissue_or_cell_type
Purified protein
Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 435–445
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human MTHFR; kinetics and structures. · source_derived_draft · unverified_draft
### folate-methyl-nadph-preference Purified full-length human MTHFR had apparent Km values of 35.5 micromolar for NADPH and 3760 micromolar for NADH. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: MTHFR strongly preferred NADPH in this assay. organism: Homo sapiens tissue_or_cell_type: Purified protein experimental_model: Recombinant human MTHFR; kinetics and structures. limitations: Affinity does not quantify cellular flux. cross_nutrient: Folate reduction uses nicotinamide reducing equivalents. [froese-2018] Structural basis for the regulation of human 5,10-methylenetetrahydrofolate reductase by phosphorylation and S-adenosylmethionine inhibition (2018). https://pubmed.ncbi.nlm.nih.gov/29891918/ DOI: 10.1038/s41467-018-04735-2
Complete structured claim and evidence
Reconstituted assays showed human MTRR sufficient to support NADPH-dependent activity of cobalamin-dependent methionine synthase.
Methionine synthase reductase / MTRR → Cobalamin-dependent methionine synthase / MTR source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B2 flavins support reactivation of B12-dependent folate/homocysteine metabolism.
evidence_location
Abstract
experimental_model
Recombinant human MTRR purification, flavin analysis, NADPH spectroscopy and methionine-synthase reconstitution.
exposure
Purified-enzyme assay
limitations
Reconstituted biochemistry; the accessible abstract identifies human MTRR but not the target MTR species. No dietary B2/B12 synergy was tested.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
The flavin reductase helps restore an enzyme that uses B12 and methylfolate.
primary_references
[olteanu2001] Human methionine synthase reductase, a soluble P-450 reductase-like dual flavoprotein, is sufficient for NADPH-dependent methionine synthase activation. (2001). https://pubmed.ncbi.nlm.nih.gov/11466310/ DOI: 10.1074/jbc.m103707200
tissue_or_cell_type
Purified recombinant enzyme; no intact tissue
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1122–1134
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human MTRR purification, flavin analysis, NADPH spectroscopy and methionine-synthase reconstitution. · source_derived_draft · unverified_draft
### b2-mtrr-mtr-reactivation Reconstituted assays showed human MTRR sufficient to support NADPH-dependent activity of cobalamin-dependent methionine synthase. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The flavin reductase helps restore an enzyme that uses B12 and methylfolate. organism: Homo sapiens tissue_or_cell_type: Purified recombinant enzyme; no intact tissue experimental_model: Recombinant human MTRR purification, flavin analysis, NADPH spectroscopy and methionine-synthase reconstitution. limitations: Reconstituted biochemistry; the accessible abstract identifies human MTRR but not the target MTR species. No dietary B2/B12 synergy was tested. exposure: Purified-enzyme assay cross_nutrient: B2 flavins support reactivation of B12-dependent folate/homocysteine metabolism. evidence_location: Abstract [olteanu2001] Human methionine synthase reductase, a soluble P-450 reductase-like dual flavoprotein, is sufficient for NADPH-dependent methionine synthase activation. (2001). https://pubmed.ncbi.nlm.nih.gov/11466310/ DOI: 10.1074/jbc.m103707200
Complete structured claim and evidence
Recombinant human RDH10 oxidized all-trans-retinol with NAD+ in microsomal assays.
Retinol dehydrogenase 10 / RDH10 → All-trans-retinal source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
NAD-dependent retinol oxidation connects vitamin A metabolism to nicotinamide redox-cofactor availability.
evidence_location
Results: cofactor preference
experimental_model
Human RDH10 in Sf9 microsomes and siRNA perturbation in human cells.
exposure
1 micromolar retinol and 1 millimolar NAD+ versus NADP+.
limitations
Cofactor specificity does not establish an effect of dietary niacin deficiency.
nutrient_topic
Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A
organism
Homo sapiens protein in Spodoptera frugiperda Sf9 cells
outcome
Recombinant human RDH10 oxidized all-trans-retinol with NAD+ in microsomal assays.
plain_language
RDH10 uses the oxidized nicotinamide cofactor to make retinal.
primary_references
[va-belyaeva-2008] Kinetic Analysis of Human Enzyme RDH10 Defines the Characteristics of a Physiologically Relevant Retinol Dehydrogenase (2008). https://pmc.ncbi.nlm.nih.gov/articles/PMC2459273/ DOI: 10.1074/jbc.M800019200
tissue_or_cell_type
Microsomes
Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 487–500
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human RDH10 in Sf9 microsomes and siRNA perturbation in human cells. · source_derived_draft · unverified_draft
### va-rdh10-retinol-oxidation Recombinant human RDH10 oxidized all-trans-retinol with NAD+ in microsomal assays. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: RDH10 uses the oxidized nicotinamide cofactor to make retinal. organism: Homo sapiens protein in Spodoptera frugiperda Sf9 cells tissue_or_cell_type: Microsomes experimental_model: Human RDH10 in Sf9 microsomes and siRNA perturbation in human cells. limitations: Cofactor specificity does not establish an effect of dietary niacin deficiency. exposure: 1 micromolar retinol and 1 millimolar NAD+ versus NADP+. outcome: Recombinant human RDH10 oxidized all-trans-retinol with NAD+ in microsomal assays. evidence_location: Results: cofactor preference cross_nutrient: NAD-dependent retinol oxidation connects vitamin A metabolism to nicotinamide redox-cofactor availability. [va-belyaeva-2008] Kinetic Analysis of Human Enzyme RDH10 Defines the Characteristics of a Physiologically Relevant Retinol Dehydrogenase (2008). https://pmc.ncbi.nlm.nih.gov/articles/PMC2459273/ DOI: 10.1074/jbc.M800019200
Complete structured claim and evidence
RDH10-activated DHRS3 reduced all-trans-retinal to retinol preferentially using NADPH.
Dehydrogenase/reductase 3 / DHRS3 → All-trans-retinol source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
NADPH supports a retinoid buffering reaction.
evidence_location
Figure 5 and Table 1
experimental_model
Human RDH10/DHRS3 coexpression in HEK293 and Sf9 cells, plus Dhrs3-null embryos.
exposure
DHRS3 coexpressed with RDH10; retinal plus NADPH.
limitations
Cofactor dependency is not a dietary niacin intervention.
nutrient_topic
Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A
organism
Homo sapiens proteins in Sf9 and HEK293 systems
outcome
RDH10-activated DHRS3 reduced all-trans-retinal to retinol preferentially using NADPH.
plain_language
This reverse step restrains retinal available for acid production.
primary_references
[va-adams-2014] The retinaldehyde reductase activity of DHRS3 is reciprocally activated by retinol dehydrogenase 10 to control retinoid homeostasis (2014). https://pmc.ncbi.nlm.nih.gov/articles/PMC4031538/ DOI: 10.1074/jbc.M114.552257
tissue_or_cell_type
Microsomal/cellular retinoid system
Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 516–529
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human RDH10/DHRS3 coexpression in HEK293 and Sf9 cells, plus Dhrs3-null embryos. · source_derived_draft · unverified_draft
### va-dhrs3-retinal-reduction RDH10-activated DHRS3 reduced all-trans-retinal to retinol preferentially using NADPH. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: This reverse step restrains retinal available for acid production. organism: Homo sapiens proteins in Sf9 and HEK293 systems tissue_or_cell_type: Microsomal/cellular retinoid system experimental_model: Human RDH10/DHRS3 coexpression in HEK293 and Sf9 cells, plus Dhrs3-null embryos. limitations: Cofactor dependency is not a dietary niacin intervention. exposure: DHRS3 coexpressed with RDH10; retinal plus NADPH. outcome: RDH10-activated DHRS3 reduced all-trans-retinal to retinol preferentially using NADPH. evidence_location: Figure 5 and Table 1 cross_nutrient: NADPH supports a retinoid buffering reaction. [va-adams-2014] The retinaldehyde reductase activity of DHRS3 is reciprocally activated by retinol dehydrogenase 10 to control retinoid homeostasis (2014). https://pmc.ncbi.nlm.nih.gov/articles/PMC4031538/ DOI: 10.1074/jbc.M114.552257
Complete structured claim and evidence
Dialyzed liver cytosol from selenium-deficient rats lost NADPH-dependent ascorbyl-radical reducing activity attributed to thioredoxin reductase.
Selenium → Ascorbyl radical reduction to ascorbate source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
true
experimental_model
Purified rat liver enzyme, dialyzed cytosol and microsomes from control/selenium-deficient rats
exposure
Dietary selenium depletion; isolated dialyzed cytosol
limitations
Activity assignment also used inhibitor sensitivity; this is a fraction assay, not a direct human outcome.
nutrient_topic
Vitamin C research collection; topical membership is not evidence of a direct dietary effect. · Vitamin C
organism
Rattus norvegicus
plain_language
Selenium deficiency impaired radical recycling in the rat liver’s soluble fraction.
primary_references
[may1998] Reduction of the ascorbyl free radical to ascorbate by thioredoxin reductase. (1998). https://pubmed.ncbi.nlm.nih.gov/9722529/ DOI: 10.1074/jbc.273.36.23039
tissue_or_cell_type
Liver cytosol
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 429–440
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified rat liver enzyme, dialyzed cytosol and microsomes from control/selenium-deficient rats · source_derived_draft · unverified_draft
### vc-transport-selenium-cytosolic-radical Dialyzed liver cytosol from selenium-deficient rats lost NADPH-dependent ascorbyl-radical reducing activity attributed to thioredoxin reductase. Condition category: nutrient_deficiency nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Selenium deficiency impaired radical recycling in the rat liver’s soluble fraction. organism: Rattus norvegicus tissue_or_cell_type: Liver cytosol experimental_model: Purified rat liver enzyme, dialyzed cytosol and microsomes from control/selenium-deficient rats limitations: Activity assignment also used inhibitor sensitivity; this is a fraction assay, not a direct human outcome. exposure: Dietary selenium depletion; isolated dialyzed cytosol cross_nutrient: true [may1998] Reduction of the ascorbyl free radical to ascorbate by thioredoxin reductase. (1998). https://pubmed.ncbi.nlm.nih.gov/9722529/ DOI: 10.1074/jbc.273.36.23039
Complete structured claim and evidence
Rat liver microsomes reduced ascorbyl radical using NADH, and this activity was insensitive to selenium depletion.
NADH → Ascorbyl radical reduction to ascorbate source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
true
experimental_model
Purified rat liver enzyme, dialyzed cytosol and microsomes from control/selenium-deficient rats
exposure
Control and selenium-deficient rat liver microsome assays
limitations
Responsible microsomal enzyme was not established in the abstract; do not assign the activity to TXNRD1.
nutrient_topic
Vitamin C research collection; topical membership is not evidence of a direct dietary effect. · Vitamin C
organism
Rattus norvegicus
plain_language
A membrane-associated recycling route remained active despite selenium shortage.
primary_references
[may1998] Reduction of the ascorbyl free radical to ascorbate by thioredoxin reductase. (1998). https://pubmed.ncbi.nlm.nih.gov/9722529/ DOI: 10.1074/jbc.273.36.23039
tissue_or_cell_type
Liver microsomal fraction
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 442–453
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified rat liver enzyme, dialyzed cytosol and microsomes from control/selenium-deficient rats · source_derived_draft · unverified_draft
### vc-transport-microsomal-radical Rat liver microsomes reduced ascorbyl radical using NADH, and this activity was insensitive to selenium depletion. Condition category: nutrient_deficiency nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: A membrane-associated recycling route remained active despite selenium shortage. organism: Rattus norvegicus tissue_or_cell_type: Liver microsomal fraction experimental_model: Purified rat liver enzyme, dialyzed cytosol and microsomes from control/selenium-deficient rats limitations: Responsible microsomal enzyme was not established in the abstract; do not assign the activity to TXNRD1. exposure: Control and selenium-deficient rat liver microsome assays cross_nutrient: true [may1998] Reduction of the ascorbyl free radical to ascorbate by thioredoxin reductase. (1998). https://pubmed.ncbi.nlm.nih.gov/9722529/ DOI: 10.1074/jbc.273.36.23039
Complete structured claim and evidence
The active human CYP27B1 reconstitution supplied human adrenodoxin reductase and NADPH upstream of human adrenodoxin.
Human ferredoxin reductase / FDXR → Human adrenodoxin / FDX1 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_location
Primary Tables 3-5, Figure 6A and Experimental procedures; full text retrieved.
experimental_model
Human protein reconstitution and substrate turnover
exposure
0.4 micromolar FDXR, 15 micromolar FDX1 and 50 micromolar NADPH; Experimental procedures.
limitations
This record reports the supported redox chain; FDXR omission or dietary niacin/riboflavin intervention was not reported in the extracted experiment.
nutrient
Vitamin D2 and D3 · Vitamin D2 and D3
nutrient_topic
Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin D2 and D3
organism
Homo sapiens proteins
plain_language
A reductase feeds the electron carrier used during vitamin D activation.
primary_references
[tang2012] Expression of human CYP27B1 in Escherichia coli and characterization in phospholipid vesicles. (2012). https://pubmed.ncbi.nlm.nih.gov/22862690/ DOI: 10.1111/j.1742-4658.2012.08736.x
tissue_or_cell_type
mitochondrial redox-partner assay
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 467–480
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human protein reconstitution and substrate turnover · source_derived_draft · unverified_draft
### vd-act-fdxr-cyp27b1-system The active human CYP27B1 reconstitution supplied human adrenodoxin reductase and NADPH upstream of human adrenodoxin. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A reductase feeds the electron carrier used during vitamin D activation. organism: Homo sapiens proteins tissue_or_cell_type: mitochondrial redox-partner assay experimental_model: Human protein reconstitution and substrate turnover limitations: This record reports the supported redox chain; FDXR omission or dietary niacin/riboflavin intervention was not reported in the extracted experiment. exposure: 0.4 micromolar FDXR, 15 micromolar FDX1 and 50 micromolar NADPH; Experimental procedures. cross_nutrient: true evidence_location: Primary Tables 3-5, Figure 6A and Experimental procedures; full text retrieved. nutrient: Vitamin D2 and D3 [tang2012] Expression of human CYP27B1 in Escherichia coli and characterization in phospholipid vesicles. (2012). https://pubmed.ncbi.nlm.nih.gov/22862690/ DOI: 10.1111/j.1742-4658.2012.08736.x
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
NAPRT knockdown reversed the rise in cellular NAD caused by nicotinic acid in the cultured human cells studied.
Human NAPRT knockdown → 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/hara2007.abstract.txt", "locator": "Indexed primary abstract", "start_char": 0, "end_char": 1634, "file_sha256": "4a605e0551bc9453dec63e8aa1e0fcd78985ae7dfca8d4b785039de0e0382547", "text_sha256": "4a605e0551bc9453dec63e8aa1e0fcd78985ae7dfca8d4b785039de0e0382547"}
experimental_model
Cultured human cells with endogenous NAPRT and experimental NAPRT knockdown; separate mouse expression measurements
exposure
NAPRT knockdown plus nicotinic acid; concentration and duration not independently available in indexed abstract
limitations
The abstract does not specify the cell line or dosing details; no inference to oral intake or patient response.
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 could not produce the same NAD rise after its entry enzyme was suppressed.
primary_references
[b3-pre-hara2007] Elevation of cellular NAD levels by nicotinic acid and involvement of nicotinic acid phosphoribosyltransferase in human cells. (2007). https://pubmed.ncbi.nlm.nih.gov/17604275/ DOI: 10.1074/jbc.m610357200
tissue_or_cell_type
Cultured human cells expressing endogenous NAPRT
trigger_kind
machinery_impairment Imported condition classification; unverified.
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 289–300
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cultured human cells with endogenous NAPRT and experimental NAPRT knockdown; separate mouse expression measurements · source_derived_draft · unverified_draft
### b3-pre-naprt-knockdown-na NAPRT knockdown reversed the rise in cellular NAD caused by nicotinic acid in the cultured human cells studied. Condition category: machinery_impairment nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Nicotinic acid could not produce the same NAD rise after its entry enzyme was suppressed. organism: Homo sapiens tissue_or_cell_type: Cultured human cells expressing endogenous NAPRT experimental_model: Cultured human cells with endogenous NAPRT and experimental NAPRT knockdown; separate mouse expression measurements limitations: The abstract does not specify the cell line or dosing details; no inference to oral intake or patient response. exposure: NAPRT knockdown plus nicotinic acid; concentration and duration not independently available in indexed abstract evidence_span: {"source_cache": "artifacts/niacin-precursors-sources/hara2007.abstract.txt", "locator": "Indexed primary abstract", "start_char": 0, "end_char": 1634, "file_sha256": "4a605e0551bc9453dec63e8aa1e0fcd78985ae7dfca8d4b785039de0e0382547", "text_sha256": "4a605e0551bc9453dec63e8aa1e0fcd78985ae7dfca8d4b785039de0e0382547"} [b3-pre-hara2007] Elevation of cellular NAD levels by nicotinic acid and involvement of nicotinic acid phosphoribosyltransferase in human cells. (2007). https://pubmed.ncbi.nlm.nih.gov/17604275/ DOI: 10.1074/jbc.m610357200
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
Purified human NADSYN1 also supported NAD+ formation with free ammonia; its reported catalytic efficiencies for glutamine and ammonia were similar, 0.45 and 0.49 per second per millimolar.
Human glutamine-dependent NAD synthetase / NADSYN1 → NAD+ source_derived_draftungraded
Experimental context and source evidence
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
Assay substrate efficiency does not show that free ammonia replaces glutamine physiologically or justify ammonia exposure.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Homo sapiens
plain_language
Human NADSYN1 can use either tested nitrogen source in vitro.
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 356–367
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-ammonia Purified human NADSYN1 also supported NAD+ formation with free ammonia; its reported catalytic efficiencies for glutamine and ammonia were similar, 0.45 and 0.49 per second per millimolar. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Human NADSYN1 can use either tested nitrogen source in vitro. 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: Assay substrate efficiency does not show that free ammonia replaces glutamine physiologically or justify ammonia exposure. exposure: Biochemical or structural assay; no dietary intervention 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 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
NMR monitoring demonstrated reversibility of the purified human NAMPT reaction; the measured equilibrium constant was 0.14 under the study conditions.
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
An isolated reaction equilibrium does not establish net intracellular salvage flux.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Homo sapiens
plain_language
This isolated chemical reaction can run in either direction.
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 382–393
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-reversible NMR monitoring demonstrated reversibility of the purified human NAMPT reaction; the measured equilibrium constant was 0.14 under the study conditions. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: This isolated chemical reaction can run in either direction. 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: An isolated reaction equilibrium does not establish net intracellular salvage flux. 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
Transient overexpression of active mouse NRK1 made NIH/3T3 fibroblasts responsive to nicotinamide riboside with increased cellular NAD+; the tested catalytically inactive kinase failed to support the response.
Mouse nicotinamide riboside kinase 1 / Nmrk1 → NAD+ source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/niacin-precursors-sources/nmrk2016.paragraphs.txt", "locator": "Normalized full-text paragraphs 7–7 (0-based)", "start_char": 5559, "end_char": 7104, "file_sha256": "fcbd5465aff51c9870d65fc9812edbad2cdf2af8bb16b6afb3170d7f0503178a", "text_sha256": "ffb453285526cec1670cc565f0b57f3893b48aba7e5014f693f09ea75079348f"}
experimental_model
Murine NRK gain/loss of function in fibroblasts and primary hepatocytes; separate human HepG2 stable-isotope experiments
exposure
Transient kinase overexpression with 4 micrograms plasmid; NR 0.5 mM for 6 h under the stated default protocol; mutant comparator NRK1-D36A or NRK2-D35A.
limitations
Forced expression in mouse fibroblasts; not a human supplementation study. Basal NAD was unchanged by active kinase overexpression without NR.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Mus musculus
plain_language
NR utilization depended on active riboside kinase in this cell model.
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 30–30 (0-based)", "start_char": 33613, "end_char": 35106, "file_sha256": "fcbd5465aff51c9870d65fc9812edbad2cdf2af8bb16b6afb3170d7f0503178a", "text_sha256": "e43865f05c251c7fbb357b31c7968056ae1b58fb1d0f4e61216e5013cb928a41"}, {"source_cache": "artifacts/niacin-precursors-sources/nmrk2016.paragraphs.txt", "locator": "Normalized full-text paragraphs 48–48 (0-based)", "start_char": 46035, "end_char": 46419, "file_sha256": "fcbd5465aff51c9870d65fc9812edbad2cdf2af8bb16b6afb3170d7f0503178a", "text_sha256": "4261a1ca6a50f8b37fd569171c8a9111b9a5ee53b2504811a46cfb40badcb90c"}]
tissue_or_cell_type
NIH/3T3 fibroblasts
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 395–407
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-mouse-nrk1-nr Transient overexpression of active mouse NRK1 made NIH/3T3 fibroblasts responsive to nicotinamide riboside with increased cellular NAD+; the tested catalytically inactive kinase failed to support the response. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: NR utilization depended on active riboside kinase in this cell model. organism: Mus musculus tissue_or_cell_type: NIH/3T3 fibroblasts experimental_model: Murine NRK gain/loss of function in fibroblasts and primary hepatocytes; separate human HepG2 stable-isotope experiments limitations: Forced expression in mouse fibroblasts; not a human supplementation study. Basal NAD was unchanged by active kinase overexpression without NR. exposure: Transient kinase overexpression with 4 micrograms plasmid; NR 0.5 mM for 6 h under the stated default protocol; mutant comparator NRK1-D36A or NRK2-D35A. evidence_span: {"source_cache": "artifacts/niacin-precursors-sources/nmrk2016.paragraphs.txt", "locator": "Normalized full-text paragraphs 7–7 (0-based)", "start_char": 5559, "end_char": 7104, "file_sha256": "fcbd5465aff51c9870d65fc9812edbad2cdf2af8bb16b6afb3170d7f0503178a", "text_sha256": "ffb453285526cec1670cc565f0b57f3893b48aba7e5014f693f09ea75079348f"} supporting_evidence_spans: [{"source_cache": "artifacts/niacin-precursors-sources/nmrk2016.paragraphs.txt", "locator": "Normalized full-text paragraphs 30–30 (0-based)", "start_char": 33613, "end_char": 35106, "file_sha256": "fcbd5465aff51c9870d65fc9812edbad2cdf2af8bb16b6afb3170d7f0503178a", "text_sha256": "e43865f05c251c7fbb357b31c7968056ae1b58fb1d0f4e61216e5013cb928a41"}, {"source_cache": "artifacts/niacin-precursors-sources/nmrk2016.paragraphs.txt", "locator": "Normalized full-text paragraphs 48–48 (0-based)", "start_char": 46035, "end_char": 46419, "file_sha256": "fcbd5465aff51c9870d65fc9812edbad2cdf2af8bb16b6afb3170d7f0503178a", "text_sha256": "4261a1ca6a50f8b37fd569171c8a9111b9a5ee53b2504811a46cfb40badcb90c"}] [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
Transient overexpression of active mouse NRK2 made NIH/3T3 fibroblasts responsive to nicotinamide riboside with increased cellular NAD+; the tested catalytically inactive kinase failed to support the response.
Mouse nicotinamide riboside kinase 2 / Nmrk2 → NAD+ source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/niacin-precursors-sources/nmrk2016.paragraphs.txt", "locator": "Normalized full-text paragraphs 7–7 (0-based)", "start_char": 5559, "end_char": 7104, "file_sha256": "fcbd5465aff51c9870d65fc9812edbad2cdf2af8bb16b6afb3170d7f0503178a", "text_sha256": "ffb453285526cec1670cc565f0b57f3893b48aba7e5014f693f09ea75079348f"}
experimental_model
Murine NRK gain/loss of function in fibroblasts and primary hepatocytes; separate human HepG2 stable-isotope experiments
exposure
Transient kinase overexpression with 4 micrograms plasmid; NR 0.5 mM for 6 h under the stated default protocol; mutant comparator NRK1-D36A or NRK2-D35A.
limitations
Forced expression in mouse fibroblasts; not a human supplementation study. Basal NAD was unchanged by active kinase overexpression without NR.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Mus musculus
plain_language
NR utilization depended on active riboside kinase in this cell model.
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 30–30 (0-based)", "start_char": 33613, "end_char": 35106, "file_sha256": "fcbd5465aff51c9870d65fc9812edbad2cdf2af8bb16b6afb3170d7f0503178a", "text_sha256": "e43865f05c251c7fbb357b31c7968056ae1b58fb1d0f4e61216e5013cb928a41"}, {"source_cache": "artifacts/niacin-precursors-sources/nmrk2016.paragraphs.txt", "locator": "Normalized full-text paragraphs 48–48 (0-based)", "start_char": 46035, "end_char": 46419, "file_sha256": "fcbd5465aff51c9870d65fc9812edbad2cdf2af8bb16b6afb3170d7f0503178a", "text_sha256": "4261a1ca6a50f8b37fd569171c8a9111b9a5ee53b2504811a46cfb40badcb90c"}]
tissue_or_cell_type
NIH/3T3 fibroblasts
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 409–421
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-mouse-nrk2-nr Transient overexpression of active mouse NRK2 made NIH/3T3 fibroblasts responsive to nicotinamide riboside with increased cellular NAD+; the tested catalytically inactive kinase failed to support the response. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: NR utilization depended on active riboside kinase in this cell model. organism: Mus musculus tissue_or_cell_type: NIH/3T3 fibroblasts experimental_model: Murine NRK gain/loss of function in fibroblasts and primary hepatocytes; separate human HepG2 stable-isotope experiments limitations: Forced expression in mouse fibroblasts; not a human supplementation study. Basal NAD was unchanged by active kinase overexpression without NR. exposure: Transient kinase overexpression with 4 micrograms plasmid; NR 0.5 mM for 6 h under the stated default protocol; mutant comparator NRK1-D36A or NRK2-D35A. evidence_span: {"source_cache": "artifacts/niacin-precursors-sources/nmrk2016.paragraphs.txt", "locator": "Normalized full-text paragraphs 7–7 (0-based)", "start_char": 5559, "end_char": 7104, "file_sha256": "fcbd5465aff51c9870d65fc9812edbad2cdf2af8bb16b6afb3170d7f0503178a", "text_sha256": "ffb453285526cec1670cc565f0b57f3893b48aba7e5014f693f09ea75079348f"} supporting_evidence_spans: [{"source_cache": "artifacts/niacin-precursors-sources/nmrk2016.paragraphs.txt", "locator": "Normalized full-text paragraphs 30–30 (0-based)", "start_char": 33613, "end_char": 35106, "file_sha256": "fcbd5465aff51c9870d65fc9812edbad2cdf2af8bb16b6afb3170d7f0503178a", "text_sha256": "e43865f05c251c7fbb357b31c7968056ae1b58fb1d0f4e61216e5013cb928a41"}, {"source_cache": "artifacts/niacin-precursors-sources/nmrk2016.paragraphs.txt", "locator": "Normalized full-text paragraphs 48–48 (0-based)", "start_char": 46035, "end_char": 46419, "file_sha256": "fcbd5465aff51c9870d65fc9812edbad2cdf2af8bb16b6afb3170d7f0503178a", "text_sha256": "4261a1ca6a50f8b37fd569171c8a9111b9a5ee53b2504811a46cfb40badcb90c"}] [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 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
In serum- and nicotinamide-free HepG2 cultures, oxygen-18-labelled NR entered intracellular NR, NMN and NAD+ pools without detectable labelled NMN or nicotinamide appearing in the medium over 24 hours.
Nicotinamide riboside → NAD+ source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/niacin-precursors-sources/nmrk2016.paragraphs.txt", "locator": "Normalized full-text paragraphs 12–12 (0-based)", "start_char": 12567, "end_char": 14130, "file_sha256": "fcbd5465aff51c9870d65fc9812edbad2cdf2af8bb16b6afb3170d7f0503178a", "text_sha256": "69b7b09a26aadc957c5bcb7c3f38cd4a426b94162ce4ff5424e98fe679c4e47c"}
experimental_model
Murine NRK gain/loss of function in fibroblasts and primary hepatocytes; separate human HepG2 stable-isotope experiments
exposure
10 micromolar oxygen-18-labelled NR; 24-hour tracing
limitations
HepG2 is a transformed cell line in specialized culture medium; does not describe oral bioavailability or every tissue.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Homo sapiens
plain_language
These cultured human liver-derived cells used intact NR as a NAD precursor.
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 38–38 (0-based)", "start_char": 39692, "end_char": 41308, "file_sha256": "fcbd5465aff51c9870d65fc9812edbad2cdf2af8bb16b6afb3170d7f0503178a", "text_sha256": "06af8996de76dd8a158899f05c337e45aa341ac5bd340a12cd041c89bc4c2d13"}]
tissue_or_cell_type
HepG2 cells
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 451–463
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-hepg2-nr-tracer In serum- and nicotinamide-free HepG2 cultures, oxygen-18-labelled NR entered intracellular NR, NMN and NAD+ pools without detectable labelled NMN or nicotinamide appearing in the medium over 24 hours. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: These cultured human liver-derived cells used intact NR as a NAD precursor. organism: Homo sapiens tissue_or_cell_type: HepG2 cells experimental_model: Murine NRK gain/loss of function in fibroblasts and primary hepatocytes; separate human HepG2 stable-isotope experiments limitations: HepG2 is a transformed cell line in specialized culture medium; does not describe oral bioavailability or every tissue. exposure: 10 micromolar oxygen-18-labelled NR; 24-hour tracing evidence_span: {"source_cache": "artifacts/niacin-precursors-sources/nmrk2016.paragraphs.txt", "locator": "Normalized full-text paragraphs 12–12 (0-based)", "start_char": 12567, "end_char": 14130, "file_sha256": "fcbd5465aff51c9870d65fc9812edbad2cdf2af8bb16b6afb3170d7f0503178a", "text_sha256": "69b7b09a26aadc957c5bcb7c3f38cd4a426b94162ce4ff5424e98fe679c4e47c"} supporting_evidence_spans: [{"source_cache": "artifacts/niacin-precursors-sources/nmrk2016.paragraphs.txt", "locator": "Normalized full-text paragraphs 38–38 (0-based)", "start_char": 39692, "end_char": 41308, "file_sha256": "fcbd5465aff51c9870d65fc9812edbad2cdf2af8bb16b6afb3170d7f0503178a", "text_sha256": "06af8996de76dd8a158899f05c337e45aa341ac5bd340a12cd041c89bc4c2d13"}] [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
Oxygen-18-labelled NMN supplied to HepG2 cultures generated extracellular labelled NR; at seven hours approximately 80% of the extracellular NMN label was present as extracellular NR.
NMN → Nicotinamide riboside source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/niacin-precursors-sources/nmrk2016.paragraphs.txt", "locator": "Normalized full-text paragraphs 12–12 (0-based)", "start_char": 12567, "end_char": 14130, "file_sha256": "fcbd5465aff51c9870d65fc9812edbad2cdf2af8bb16b6afb3170d7f0503178a", "text_sha256": "69b7b09a26aadc957c5bcb7c3f38cd4a426b94162ce4ff5424e98fe679c4e47c"}
experimental_model
Murine NRK gain/loss of function in fibroblasts and primary hepatocytes; separate human HepG2 stable-isotope experiments
exposure
10 micromolar labelled NMN, sampled over 24 h; reported seven-hour comparison
limitations
Supports extracellular conversion in this model. It does not settle possible intact NMN transport in all tissues or identify a specific phosphatase.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Homo sapiens
plain_language
NMN was processed outside these cells into the riboside precursor.
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 38–38 (0-based)", "start_char": 39692, "end_char": 41308, "file_sha256": "fcbd5465aff51c9870d65fc9812edbad2cdf2af8bb16b6afb3170d7f0503178a", "text_sha256": "06af8996de76dd8a158899f05c337e45aa341ac5bd340a12cd041c89bc4c2d13"}]
tissue_or_cell_type
HepG2 cells in serum- and nicotinamide-free medium
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 465–477
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-hepg2-nmn-extracellular-nr Oxygen-18-labelled NMN supplied to HepG2 cultures generated extracellular labelled NR; at seven hours approximately 80% of the extracellular NMN label was present as extracellular NR. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: NMN was processed outside these cells into the riboside precursor. organism: Homo sapiens tissue_or_cell_type: HepG2 cells in serum- and nicotinamide-free medium experimental_model: Murine NRK gain/loss of function in fibroblasts and primary hepatocytes; separate human HepG2 stable-isotope experiments limitations: Supports extracellular conversion in this model. It does not settle possible intact NMN transport in all tissues or identify a specific phosphatase. exposure: 10 micromolar labelled NMN, sampled over 24 h; reported seven-hour comparison evidence_span: {"source_cache": "artifacts/niacin-precursors-sources/nmrk2016.paragraphs.txt", "locator": "Normalized full-text paragraphs 12–12 (0-based)", "start_char": 12567, "end_char": 14130, "file_sha256": "fcbd5465aff51c9870d65fc9812edbad2cdf2af8bb16b6afb3170d7f0503178a", "text_sha256": "69b7b09a26aadc957c5bcb7c3f38cd4a426b94162ce4ff5424e98fe679c4e47c"} supporting_evidence_spans: [{"source_cache": "artifacts/niacin-precursors-sources/nmrk2016.paragraphs.txt", "locator": "Normalized full-text paragraphs 38–38 (0-based)", "start_char": 39692, "end_char": 41308, "file_sha256": "fcbd5465aff51c9870d65fc9812edbad2cdf2af8bb16b6afb3170d7f0503178a", "text_sha256": "06af8996de76dd8a158899f05c337e45aa341ac5bd340a12cd041c89bc4c2d13"}] [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
Human TDO2 substrate and product structures support oxidative conversion of L-tryptophan and oxygen to N-formylkynurenine.
Human tryptophan 2,3-dioxygenase / TDO2 → N-Formyl-L-kynurenine source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Tryptophan provides the carbon framework entering the de novo niacin pathway; downstream steps remain necessary.
evidence_span
{"source_cache": "artifacts/niacin-precursors-sources/tdo2016.paragraphs.txt", "locator": "Normalized full-text paragraphs 9–9 (0-based)", "start_char": 8003, "end_char": 9136, "file_sha256": "3f91886745b8ff9fb808232c839dd346b03605dd025d5fa682a3de4f81338ec5", "text_sha256": "b39e2ce5d405e5eb8fde25aec369c306954365d7ec2b448fe5a5689e89785e2a"}
experimental_model
Purified human TDO2 crystallography and spectroscopy; substrate/product complexes
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
TDO2 opens the tryptophan ring at the beginning of the kynurenine route.
primary_references
[b3-pre-tdo2016] Molecular basis for catalysis and substrate-mediated cellular stabilization of human tryptophan 2,3-dioxygenase. (2016). https://pubmed.ncbi.nlm.nih.gov/27762317/ DOI: 10.1038/srep35169
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 479–491
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human TDO2 crystallography and spectroscopy; substrate/product complexes · source_derived_draft · unverified_draft
### b3-pre-tdo-reaction Human TDO2 substrate and product structures support oxidative conversion of L-tryptophan and oxygen to N-formylkynurenine. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: TDO2 opens the tryptophan ring at the beginning of the kynurenine route. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Purified human TDO2 crystallography and spectroscopy; substrate/product complexes limitations: Purified-enzyme evidence does not establish dietary intake requirements or clinical outcomes. exposure: Biochemical or structural assay; no dietary intervention cross_nutrient: Tryptophan provides the carbon framework entering the de novo niacin pathway; downstream steps remain necessary. evidence_span: {"source_cache": "artifacts/niacin-precursors-sources/tdo2016.paragraphs.txt", "locator": "Normalized full-text paragraphs 9–9 (0-based)", "start_char": 8003, "end_char": 9136, "file_sha256": "3f91886745b8ff9fb808232c839dd346b03605dd025d5fa682a3de4f81338ec5", "text_sha256": "b39e2ce5d405e5eb8fde25aec369c306954365d7ec2b448fe5a5689e89785e2a"} [b3-pre-tdo2016] Molecular basis for catalysis and substrate-mediated cellular stabilization of human tryptophan 2,3-dioxygenase. (2016). https://pubmed.ncbi.nlm.nih.gov/27762317/ DOI: 10.1038/srep35169
Complete structured claim and evidence
In the human TDO2 substrate complex, molecular oxygen was coordinated to the heme iron next to the L-tryptophan substrate.
Heme → Human tryptophan 2,3-dioxygenase / TDO2 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Heme iron participates in a tryptophan-to-niacin upstream enzyme; the structure does not establish a dietary iron threshold.
evidence_span
{"source_cache": "artifacts/niacin-precursors-sources/tdo2016.paragraphs.txt", "locator": "Normalized full-text paragraphs 7–7 (0-based)", "start_char": 5512, "end_char": 7250, "file_sha256": "3f91886745b8ff9fb808232c839dd346b03605dd025d5fa682a3de4f81338ec5", "text_sha256": "057137936657c739cdef730f5d10b930ec40af5e09f0ed4e2abbd813f26db9f0"}
experimental_model
Purified human TDO2 crystallography and spectroscopy; substrate/product complexes
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
Iron held in heme positions oxygen for this precursor reaction.
primary_references
[b3-pre-tdo2016] Molecular basis for catalysis and substrate-mediated cellular stabilization of human tryptophan 2,3-dioxygenase. (2016). https://pubmed.ncbi.nlm.nih.gov/27762317/ DOI: 10.1038/srep35169
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 493–505
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human TDO2 crystallography and spectroscopy; substrate/product complexes · source_derived_draft · unverified_draft
### b3-pre-tdo-heme-oxygen In the human TDO2 substrate complex, molecular oxygen was coordinated to the heme iron next to the L-tryptophan substrate. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Iron held in heme positions oxygen for this precursor reaction. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Purified human TDO2 crystallography and spectroscopy; substrate/product complexes limitations: Purified-enzyme evidence does not establish dietary intake requirements or clinical outcomes. exposure: Biochemical or structural assay; no dietary intervention cross_nutrient: Heme iron participates in a tryptophan-to-niacin upstream enzyme; the structure does not establish a dietary iron threshold. evidence_span: {"source_cache": "artifacts/niacin-precursors-sources/tdo2016.paragraphs.txt", "locator": "Normalized full-text paragraphs 7–7 (0-based)", "start_char": 5512, "end_char": 7250, "file_sha256": "3f91886745b8ff9fb808232c839dd346b03605dd025d5fa682a3de4f81338ec5", "text_sha256": "057137936657c739cdef730f5d10b930ec40af5e09f0ed4e2abbd813f26db9f0"} [b3-pre-tdo2016] Molecular basis for catalysis and substrate-mediated cellular stabilization of human tryptophan 2,3-dioxygenase. (2016). https://pubmed.ncbi.nlm.nih.gov/27762317/ DOI: 10.1038/srep35169
Complete structured claim and evidence
Crystallography and metal characterization identified iron in the active site of human HAAO, with spectroscopic behavior consistent with the ferrous preparation before air oxidation.
Ferrous iron → Human 3-hydroxyanthranilate 3,4-dioxygenase / HAAO source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Nonheme iron participates in a downstream tryptophan/niacin pathway enzyme; nutritional iron restriction was not tested.
evidence_span
{"source_cache": "artifacts/niacin-precursors-sources/haao2017.paragraphs.txt", "locator": "Normalized full-text paragraphs 33–33 (0-based)", "start_char": 22514, "end_char": 24337, "file_sha256": "d02386a59595104ccae2e62943e69030930da86ec005769b469f2001e31a6eb5", "text_sha256": "4c47aa3f5cdc1fd3c776752c345f1d60e4833d0e3b7e8227c574ae086c3b1783"}
experimental_model
Purified human HAAO metal-containing crystal structures and ICP-MS/XRF/EPR characterization
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
A second iron-containing enzyme acts farther along the tryptophan route.
primary_references
[b3-pre-haao2017] Crystal structures of human 3-hydroxyanthranilate 3,4-dioxygenase with native and non-native metals bound in the active site. (2017). https://pubmed.ncbi.nlm.nih.gov/28375145/ DOI: 10.1107/s2059798317002029
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 507–519
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human HAAO metal-containing crystal structures and ICP-MS/XRF/EPR characterization · source_derived_draft · unverified_draft
### b3-pre-haao-iron Crystallography and metal characterization identified iron in the active site of human HAAO, with spectroscopic behavior consistent with the ferrous preparation before air oxidation. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A second iron-containing enzyme acts farther along the tryptophan route. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Purified human HAAO metal-containing crystal structures and ICP-MS/XRF/EPR characterization limitations: Purified-enzyme evidence does not establish dietary intake requirements or clinical outcomes. exposure: Biochemical or structural assay; no dietary intervention cross_nutrient: Nonheme iron participates in a downstream tryptophan/niacin pathway enzyme; nutritional iron restriction was not tested. evidence_span: {"source_cache": "artifacts/niacin-precursors-sources/haao2017.paragraphs.txt", "locator": "Normalized full-text paragraphs 33–33 (0-based)", "start_char": 22514, "end_char": 24337, "file_sha256": "d02386a59595104ccae2e62943e69030930da86ec005769b469f2001e31a6eb5", "text_sha256": "4c47aa3f5cdc1fd3c776752c345f1d60e4833d0e3b7e8227c574ae086c3b1783"} [b3-pre-haao2017] Crystal structures of human 3-hydroxyanthranilate 3,4-dioxygenase with native and non-native metals bound in the active site. (2017). https://pubmed.ncbi.nlm.nih.gov/28375145/ DOI: 10.1107/s2059798317002029
Complete structured claim and evidence
Human HAAO expressed in HEK-293 cells was enzymatically active toward 3-hydroxyanthranilate, with an apparent substrate Km near 2 micromolar in the study of the quinolinate-producing pathway step.
Human 3-hydroxyanthranilate 3,4-dioxygenase / HAAO → Quinolinic acid source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
This step follows the canonical PLP-dependent KYNU reaction and uses a nonheme iron enzyme.
evidence_span
{"source_cache": "artifacts/niacin-precursors-sources/haao1994.abstract.txt", "locator": "Indexed primary abstract", "start_char": 0, "end_char": 1874, "file_sha256": "a79697b138bcb2957b0eff9580266c7879a1c5853aba34898f891559b4e435f8", "text_sha256": "a79697b138bcb2957b0eff9580266c7879a1c5853aba34898f891559b4e435f8"}
experimental_model
Human HAAO cDNA from HepG2 library, expressed in HEK-293 cells and assayed biochemically
exposure
Biochemical or structural assay; no dietary intervention
limitations
The immediate HAAO product is ACMS, which cyclizes to quinolinate; the indexed abstract uses pathway-level quinolinate wording. This claim does not assert direct NAD+ synthesis.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Homo sapiens
plain_language
Expressed human HAAO processed the product made by B6-dependent KYNU.
primary_references
[b3-pre-haao1994] Molecular cloning and functional expression of human 3-hydroxyanthranilic-acid dioxygenase. (1994). https://pubmed.ncbi.nlm.nih.gov/7514594/ DOI: 10.1016/s0021-9258(17)36717-0 [b3-pre-haao2017] Crystal structures of human 3-hydroxyanthranilate 3,4-dioxygenase with native and non-native metals bound in the active site. (2017). https://pubmed.ncbi.nlm.nih.gov/28375145/ DOI: 10.1107/s2059798317002029
supporting_evidence_spans
[{"source_cache": "artifacts/niacin-precursors-sources/haao2017.paragraphs.txt", "locator": "Normalized full-text paragraphs 14–14 (0-based)", "start_char": 4395, "end_char": 7197, "file_sha256": "d02386a59595104ccae2e62943e69030930da86ec005769b469f2001e31a6eb5", "text_sha256": "3b52b56d1b671c24721b47204cd30d19cd004f8a461fecd4875e94d3f491dbf6"}]
tissue_or_cell_type
HEK-293 cells expressing human HAAO; biochemical activity assay
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 521–535
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human HAAO cDNA from HepG2 library, expressed in HEK-293 cells and assayed biochemically · source_derived_draft · unverified_draft
### b3-pre-haao-human-activity Human HAAO expressed in HEK-293 cells was enzymatically active toward 3-hydroxyanthranilate, with an apparent substrate Km near 2 micromolar in the study of the quinolinate-producing pathway step. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Expressed human HAAO processed the product made by B6-dependent KYNU. organism: Homo sapiens tissue_or_cell_type: HEK-293 cells expressing human HAAO; biochemical activity assay experimental_model: Human HAAO cDNA from HepG2 library, expressed in HEK-293 cells and assayed biochemically limitations: The immediate HAAO product is ACMS, which cyclizes to quinolinate; the indexed abstract uses pathway-level quinolinate wording. This claim does not assert direct NAD+ synthesis. exposure: Biochemical or structural assay; no dietary intervention cross_nutrient: This step follows the canonical PLP-dependent KYNU reaction and uses a nonheme iron enzyme. evidence_span: {"source_cache": "artifacts/niacin-precursors-sources/haao1994.abstract.txt", "locator": "Indexed primary abstract", "start_char": 0, "end_char": 1874, "file_sha256": "a79697b138bcb2957b0eff9580266c7879a1c5853aba34898f891559b4e435f8", "text_sha256": "a79697b138bcb2957b0eff9580266c7879a1c5853aba34898f891559b4e435f8"} supporting_evidence_spans: [{"source_cache": "artifacts/niacin-precursors-sources/haao2017.paragraphs.txt", "locator": "Normalized full-text paragraphs 14–14 (0-based)", "start_char": 4395, "end_char": 7197, "file_sha256": "d02386a59595104ccae2e62943e69030930da86ec005769b469f2001e31a6eb5", "text_sha256": "3b52b56d1b671c24721b47204cd30d19cd004f8a461fecd4875e94d3f491dbf6"}] [b3-pre-haao1994] Molecular cloning and functional expression of human 3-hydroxyanthranilic-acid dioxygenase. (1994). https://pubmed.ncbi.nlm.nih.gov/7514594/ DOI: 10.1016/s0021-9258(17)36717-0 [b3-pre-haao2017] Crystal structures of human 3-hydroxyanthranilate 3,4-dioxygenase with native and non-native metals bound in the active site. (2017). https://pubmed.ncbi.nlm.nih.gov/28375145/ DOI: 10.1107/s2059798317002029
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
Human SIRT2 deacetylated monoacetylated histone peptides in the NAD-consuming reaction producing nicotinamide and O-acetyl-ADP-ribose.
Human SIRT2 → Monoacetylated histone H3/H4 assay peptides source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
evidence_span
{"source_cache": "artifacts/niacin-consumption-sources/sirt22004.abstract.txt", "locator": "Indexed abstract", "start_char": 0, "end_char": 1423, "file_sha256": "a84f7d25c6e518d3317d4b0a41df8d8ac447cd3ef2966815c9818ca63116ef7f", "text_sha256": "a84f7d25c6e518d3317d4b0a41df8d8ac447cd3ef2966815c9818ca63116ef7f"}
experimental_model
Recombinant enzyme and monoacetylated histone H3/H4 peptide assays
exposure
Human SIRT2; yeast Sir2/Hst2 were also studied separately
limitations
Indexed abstract; rapid-kinetic details are not assigned to human SIRT2 individually. No dietary or longevity inference.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Human
plain_language
SIRT2 consumes NAD while removing acetyl groups from histone peptides.
primary_references
[b3-cons-sirt22004] Substrate specificity and kinetic mechanism of the Sir2 family of NAD+-dependent histone/protein deacetylases. (2004). https://pubmed.ncbi.nlm.nih.gov/15274642/ DOI: 10.1021/bi049592e
tissue_or_cell_type
Cell-free assay
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 551–563
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant enzyme and monoacetylated histone H3/H4 peptide assays · source_derived_draft · unverified_draft
### b3-cons-sirt2-reaction Human SIRT2 deacetylated monoacetylated histone peptides in the NAD-consuming reaction producing nicotinamide and O-acetyl-ADP-ribose. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: SIRT2 consumes NAD while removing acetyl groups from histone peptides. organism: Human tissue_or_cell_type: Cell-free assay experimental_model: Recombinant enzyme and monoacetylated histone H3/H4 peptide assays limitations: Indexed abstract; rapid-kinetic details are not assigned to human SIRT2 individually. No dietary or longevity inference. exposure: Human SIRT2; yeast Sir2/Hst2 were also studied separately cross_nutrient: false evidence_span: {"source_cache": "artifacts/niacin-consumption-sources/sirt22004.abstract.txt", "locator": "Indexed abstract", "start_char": 0, "end_char": 1423, "file_sha256": "a84f7d25c6e518d3317d4b0a41df8d8ac447cd3ef2966815c9818ca63116ef7f", "text_sha256": "a84f7d25c6e518d3317d4b0a41df8d8ac447cd3ef2966815c9818ca63116ef7f"} [b3-cons-sirt22004] Substrate specificity and kinetic mechanism of the Sir2 family of NAD+-dependent histone/protein deacetylases. (2004). https://pubmed.ncbi.nlm.nih.gov/15274642/ DOI: 10.1021/bi049592e
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
Human CD38 also hydrolyzes cyclic ADP-ribose to ADP-ribose.
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
Cyclic ADP-ribose 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 also breaks down cyclic ADP-ribose.
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 593–605
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-cadpr-hydrolysis Human CD38 also hydrolyzes cyclic ADP-ribose to ADP-ribose. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: CD38 also breaks down cyclic ADP-ribose. 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: Cyclic ADP-ribose 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
Extracellular cyclic ADP-ribose generated by human CD38-expressing COS1 cells was detected by calcium release from sea-urchin egg microsomes.
Cyclic ADP-ribose → Intracellular calcium-store release source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_span
{"source_cache": "artifacts/niacin-consumption-sources/cd381993.abstract.txt", "locator": "Indexed abstract", "start_char": 0, "end_char": 540, "file_sha256": "e8ba405a5300f922bcf34c358d95735b86637331f4cf15a009ac5bf8df93f1e5", "text_sha256": "e8ba405a5300f922bcf34c358d95735b86637331f4cf15a009ac5bf8df93f1e5"}
experimental_model
Human CD38 expression in monkey COS1 cells with sea-urchin microsome bioassay
exposure
CD38 cDNA transfection; NAD+ extracellular substrate
limitations
This mixed-species bioassay does not demonstrate intracellular trafficking of extracellular cADPR or calcium regulation after oral niacin.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Human protein; African green monkey cells; sea urchin microsomes
plain_language
A CD38-generated messenger mobilized calcium in an egg-microsome bioassay.
primary_references
[b3-cons-cd381993] Human lymphocyte antigen CD38 catalyzes the production of cyclic ADP-ribose. (1993). https://pubmed.ncbi.nlm.nih.gov/8253202/ DOI: 10.1016/0014-5793(93)80735-d
tissue_or_cell_type
COS1 kidney-cell culture; sea-urchin egg microsomes
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 607–619
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human CD38 expression in monkey COS1 cells with sea-urchin microsome bioassay · source_derived_draft · unverified_draft
### b3-cons-cadpr-store-calcium Extracellular cyclic ADP-ribose generated by human CD38-expressing COS1 cells was detected by calcium release from sea-urchin egg microsomes. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A CD38-generated messenger mobilized calcium in an egg-microsome bioassay. organism: Human protein; African green monkey cells; sea urchin microsomes tissue_or_cell_type: COS1 kidney-cell culture; sea-urchin egg microsomes experimental_model: Human CD38 expression in monkey COS1 cells with sea-urchin microsome bioassay limitations: This mixed-species bioassay does not demonstrate intracellular trafficking of extracellular cADPR or calcium regulation after oral niacin. exposure: CD38 cDNA transfection; NAD+ extracellular substrate cross_nutrient: true evidence_span: {"source_cache": "artifacts/niacin-consumption-sources/cd381993.abstract.txt", "locator": "Indexed abstract", "start_char": 0, "end_char": 540, "file_sha256": "e8ba405a5300f922bcf34c358d95735b86637331f4cf15a009ac5bf8df93f1e5", "text_sha256": "e8ba405a5300f922bcf34c358d95735b86637331f4cf15a009ac5bf8df93f1e5"} [b3-cons-cd381993] Human lymphocyte antigen CD38 catalyzes the production of cyclic ADP-ribose. (1993). https://pubmed.ncbi.nlm.nih.gov/8253202/ DOI: 10.1016/0014-5793(93)80735-d
Complete structured claim and evidence
Intracellular free ADP-ribose gated calcium-permeable currents in HEK293 cells expressing human TRPM2/LTRPC2.
ADP-ribose → Human TRPM2 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_span
{"source_cache": "artifacts/niacin-consumption-sources/trpm2001.abstract.txt", "locator": "Indexed abstract", "start_char": 0, "end_char": 964, "file_sha256": "960106d86cb7e891772139bf3b6339a1e50129c93a9e3517ebc7b86d61b4178e", "text_sha256": "960106d86cb7e891772139bf3b6339a1e50129c93a9e3517ebc7b86d61b4178e"}
experimental_model
Whole-cell and single-channel electrophysiology
exposure
Intracellular free ADP-ribose
limitations
This establishes channel gating in the assay, not that all NAD cleavage causes calcium influx in vivo.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Human
plain_language
Free ADP-ribose can open a channel that conducts calcium.
primary_references
[b3-cons-trpm2001] ADP-ribose gating of the calcium-permeable LTRPC2 channel revealed by Nudix motif homology. (2001). https://pubmed.ncbi.nlm.nih.gov/11385575/ DOI: 10.1038/35079100
tissue_or_cell_type
HEK293 cells expressing recombinant TRPM2
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 621–633
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Whole-cell and single-channel electrophysiology · source_derived_draft · unverified_draft
### b3-cons-adpr-trpm2-gating Intracellular free ADP-ribose gated calcium-permeable currents in HEK293 cells expressing human TRPM2/LTRPC2. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Free ADP-ribose can open a channel that conducts calcium. organism: Human tissue_or_cell_type: HEK293 cells expressing recombinant TRPM2 experimental_model: Whole-cell and single-channel electrophysiology limitations: This establishes channel gating in the assay, not that all NAD cleavage causes calcium influx in vivo. exposure: Intracellular free ADP-ribose cross_nutrient: true evidence_span: {"source_cache": "artifacts/niacin-consumption-sources/trpm2001.abstract.txt", "locator": "Indexed abstract", "start_char": 0, "end_char": 964, "file_sha256": "960106d86cb7e891772139bf3b6339a1e50129c93a9e3517ebc7b86d61b4178e", "text_sha256": "960106d86cb7e891772139bf3b6339a1e50129c93a9e3517ebc7b86d61b4178e"} [b3-cons-trpm2001] ADP-ribose gating of the calcium-permeable LTRPC2 channel revealed by Nudix motif homology. (2001). https://pubmed.ncbi.nlm.nih.gov/11385575/ DOI: 10.1038/35079100
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
PARP2 combined with HPF1 supported serine ADP-ribosylation of histones in NAD+-containing reconstitutions.
Human PARP2 → Histone 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 35", "start_char": 11457, "end_char": 12178, "file_sha256": "8195abaa884a41856a21fb1d4e7ee376ce80424f11f4625ca4d597a717cef30e", "text_sha256": "289a0535244252fc3cffaceacc16ceadfa35b407b293f797cb094f2102746f19"}
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
PARP2 can also transfer ADP-ribose to histone serines with HPF1.
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 649–661
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-parp2-histone-serine PARP2 combined with HPF1 supported serine ADP-ribosylation of histones in NAD+-containing reconstitutions. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: PARP2 can also transfer ADP-ribose to histone serines with HPF1. 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 35", "start_char": 11457, "end_char": 12178, "file_sha256": "8195abaa884a41856a21fb1d4e7ee376ce80424f11f4625ca4d597a717cef30e", "text_sha256": "289a0535244252fc3cffaceacc16ceadfa35b407b293f797cb094f2102746f19"} [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
HPF1-null U2OS cells showed near-loss of histone serine ADP-ribosylation after hydrogen-peroxide-induced DNA damage.
Human HPF1 knockout genotype → Histone serine ADP-ribosylation source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
false
evidence_span
{"source_cache": "artifacts/niacin-consumption-sources/parp2017.txt", "locator": "Full text, normalized paragraph 36", "start_char": 12179, "end_char": 12883, "file_sha256": "8195abaa884a41856a21fb1d4e7ee376ce80424f11f4625ca4d597a717cef30e", "text_sha256": "a36d5aa7fb74cd3100332088b118c7c3d97951e35641dd7eed75ea4aa47ed9ee"}
experimental_model
SILAC proteomics comparing wild-type and HPF1-null U2OS cells
exposure
HPF1 gene deletion; H2O2 DNA damage
limitations
Some abundant H2B peptides retained very small signals; this is not literal proof of zero modification or dietary NAD deficiency.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Human
plain_language
Removing HPF1 largely eliminated this histone modification after experimental DNA damage.
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
U2OS osteosarcoma cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 663–675
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · SILAC proteomics comparing wild-type and HPF1-null U2OS cells · source_derived_draft · unverified_draft
### b3-cons-hpf1-loss-histone-adpr HPF1-null U2OS cells showed near-loss of histone serine ADP-ribosylation after hydrogen-peroxide-induced DNA damage. Condition category: machinery_impairment nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Removing HPF1 largely eliminated this histone modification after experimental DNA damage. organism: Human tissue_or_cell_type: U2OS osteosarcoma cells experimental_model: SILAC proteomics comparing wild-type and HPF1-null U2OS cells limitations: Some abundant H2B peptides retained very small signals; this is not literal proof of zero modification or dietary NAD deficiency. exposure: HPF1 gene deletion; H2O2 DNA damage cross_nutrient: false evidence_span: {"source_cache": "artifacts/niacin-consumption-sources/parp2017.txt", "locator": "Full text, normalized paragraph 36", "start_char": 12179, "end_char": 12883, "file_sha256": "8195abaa884a41856a21fb1d4e7ee376ce80424f11f4625ca4d597a717cef30e", "text_sha256": "a36d5aa7fb74cd3100332088b118c7c3d97951e35641dd7eed75ea4aa47ed9ee"} [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
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
Human SARM1 TIR-domain NAD+ cleavage also generated cyclic ADP-ribose as a minor product.
Human SARM1 TIR-domain construct → Cyclic ADP-ribose 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. Drosophila product ratios differed and are not generalized to humans.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Human
plain_language
The human SARM1 reaction also makes some cyclic ADP-ribose.
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 691–703
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-cadpr Human SARM1 TIR-domain NAD+ cleavage also generated cyclic ADP-ribose as a minor product. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The human SARM1 reaction also makes some cyclic ADP-ribose. 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. Drosophila product ratios differed and are not generalized to humans. 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
Nicotinamide inhibited purified human SARM1 TIR NADase activity, with an assay IC50 of 43.8 micromolar.
Nicotinamide → Human SARM1 TIR-domain construct 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 25", "start_char": 16947, "end_char": 18260, "file_sha256": "fc30de231911f5c30425173d684495e62c725ba27c78d44592e6bc68433ef545", "text_sha256": "bf110010a793c4d1d3c263db9f213aa5d539bcf1501265fe30fb1ab9ed4028fa"}
experimental_model
Purified domain dose-response assay
exposure
Nicotinamide titration; starting NAD+ about 5 micromolar
limitations
Purified engineered TIR fragment rather than basal activity of intact full-length SARM1; no dietary dose inference. IC50 depends on assay conditions and is not a therapeutic plasma target.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Human
plain_language
A product of NAD cleavage fed back to inhibit the isolated SARM1 domain.
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 705–717
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified domain dose-response assay · source_derived_draft · unverified_draft
### b3-cons-nicotinamide-sarm-inhibition Nicotinamide inhibited purified human SARM1 TIR NADase activity, with an assay IC50 of 43.8 micromolar. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A product of NAD cleavage fed back to inhibit the isolated SARM1 domain. organism: Human tissue_or_cell_type: Cell-free preparation experimental_model: Purified domain dose-response assay limitations: Purified engineered TIR fragment rather than basal activity of intact full-length SARM1; no dietary dose inference. IC50 depends on assay conditions and is not a therapeutic plasma target. exposure: Nicotinamide titration; starting NAD+ about 5 micromolar cross_nutrient: false evidence_span: {"source_cache": "artifacts/niacin-consumption-sources/sarm2017.txt", "locator": "Full text, normalized paragraph 25", "start_char": 16947, "end_char": 18260, "file_sha256": "fc30de231911f5c30425173d684495e62c725ba27c78d44592e6bc68433ef545", "text_sha256": "bf110010a793c4d1d3c263db9f213aa5d539bcf1501265fe30fb1ab9ed4028fa"} [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
The human SARM1 TIR E642A mutant failed to cleave NAD+ in the cell-free NADase assay.
Human SARM1 TIR E642A construct → NAD+ source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
false
evidence_span
{"source_cache": "artifacts/niacin-consumption-sources/sarm2017.txt", "locator": "Full text, normalized paragraph 27", "start_char": 18354, "end_char": 20343, "file_sha256": "fc30de231911f5c30425173d684495e62c725ba27c78d44592e6bc68433ef545", "text_sha256": "eda6dc283d30b48f68dc8626f2ea00ffb36d08cf8597eb6e7b1ce7e091fd0cb3"}
experimental_model
Cell-free translation, purification and NADase assay
exposure
E642A compared with wild-type TIR
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
Changing a catalytic glutamate disabled NAD cleavage in the assay.
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
Purified human mutant domain
trigger_kind
machinery_impairment Imported condition classification; unverified.
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 719–731
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell-free translation, purification and NADase assay · source_derived_draft · unverified_draft
### b3-cons-sarm-e642a-loss The human SARM1 TIR E642A mutant failed to cleave NAD+ in the cell-free NADase assay. Condition category: machinery_impairment nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Changing a catalytic glutamate disabled NAD cleavage in the assay. organism: Human tissue_or_cell_type: Purified human mutant domain experimental_model: Cell-free translation, purification and NADase assay limitations: Purified engineered TIR fragment rather than basal activity of intact full-length SARM1; no dietary dose inference. exposure: E642A compared with wild-type TIR cross_nutrient: false evidence_span: {"source_cache": "artifacts/niacin-consumption-sources/sarm2017.txt", "locator": "Full text, normalized paragraph 27", "start_char": 18354, "end_char": 20343, "file_sha256": "fc30de231911f5c30425173d684495e62c725ba27c78d44592e6bc68433ef545", "text_sha256": "eda6dc283d30b48f68dc8626f2ea00ffb36d08cf8597eb6e7b1ce7e091fd0cb3"} [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
After axotomy of Sarm1-null mouse DRG neurons, re-expression of active human SARM1 restored rapid axonal NAD+ depletion, whereas E642A did not.
Human SARM1 E642A → Axonal NAD+ concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
false
evidence_span
{"source_cache": "artifacts/niacin-consumption-sources/sarm2017.txt", "locator": "Full text, normalized paragraph 29", "start_char": 20432, "end_char": 22775, "file_sha256": "fc30de231911f5c30425173d684495e62c725ba27c78d44592e6bc68433ef545", "text_sha256": "e75c162a4b5f51b7e6ef5e20612ed8ebfbe035a41abf81284cb055dfcf860333"}
experimental_model
Reconstitution of Sarm1-null E13.5 mouse DRG neurons with SARM1 constructs
exposure
Lentiviral transduction on DIV1; axotomy on DIV7
limitations
Human protein was expressed in mouse neurons; injury model, not nutritional depletion or proof of human therapeutic benefit.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Human construct in mouse neurons
plain_language
The catalytic mutant spared axonal NAD after experimental nerve injury.
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
Cultured dorsal-root-ganglion axons
trigger_kind
machinery_impairment Imported condition classification; unverified.
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 733–745
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Reconstitution of Sarm1-null E13.5 mouse DRG neurons with SARM1 constructs · source_derived_draft · unverified_draft
### b3-cons-sarm-axotomy-nad After axotomy of Sarm1-null mouse DRG neurons, re-expression of active human SARM1 restored rapid axonal NAD+ depletion, whereas E642A did not. Condition category: machinery_impairment nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The catalytic mutant spared axonal NAD after experimental nerve injury. organism: Human construct in mouse neurons tissue_or_cell_type: Cultured dorsal-root-ganglion axons experimental_model: Reconstitution of Sarm1-null E13.5 mouse DRG neurons with SARM1 constructs limitations: Human protein was expressed in mouse neurons; injury model, not nutritional depletion or proof of human therapeutic benefit. exposure: Lentiviral transduction on DIV1; axotomy on DIV7 cross_nutrient: false evidence_span: {"source_cache": "artifacts/niacin-consumption-sources/sarm2017.txt", "locator": "Full text, normalized paragraph 29", "start_char": 20432, "end_char": 22775, "file_sha256": "fc30de231911f5c30425173d684495e62c725ba27c78d44592e6bc68433ef545", "text_sha256": "e75c162a4b5f51b7e6ef5e20612ed8ebfbe035a41abf81284cb055dfcf860333"} [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
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
NNMT overexpression raised cellular SAH relative to GFP or inactive-NNMT controls in the tested human cancer-cell models.
Human NNMT → Cellular S-adenosylhomocysteine 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
Stable NNMT overexpression; 100 micromolar methionine medium and lower-methionine 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
Extra NNMT activity increased the methyl-transfer coproduct SAH.
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 renal carcinoma; MUM2C and OVCAR3 comparisons
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 761–773
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-sah-increase NNMT overexpression raised cellular SAH relative to GFP or inactive-NNMT controls in the tested human cancer-cell models. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Extra NNMT activity increased the methyl-transfer coproduct SAH. organism: Human tissue_or_cell_type: 769P renal carcinoma; MUM2C and OVCAR3 comparisons 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: Stable NNMT overexpression; 100 micromolar methionine medium and lower-methionine comparisons 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
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 10–20 micromolar medium methionine, NNMT-overexpressing 769P cells had reduced methylation of several histone lysine marks compared with controls.
Human NNMT → Histone methylation 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 35", "start_char": 19327, "end_char": 21089, "file_sha256": "7d88fd656ba772962185234a9bd021e40a9b83f9156db836f723eba06b68acca", "text_sha256": "5b6ea17ec741ecc064f97de9d83d49809db5e62588ffc1164e6e771fc9fc50c3"}
experimental_model
Immunoblotting of histone methylation in engineered cells
exposure
NNMT overexpression; 10 or 20 micromolar methionine; GFP and inactive NNMT controls
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. Not every histone mark changed; this does not establish global DNA hypomethylation.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Human
plain_language
NNMT changed several histone methylation marks in this culture model.
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 803–815
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Immunoblotting of histone methylation in engineered cells · source_derived_draft · unverified_draft
### b3-cons-nnmt-histone-methylation At 10–20 micromolar medium methionine, NNMT-overexpressing 769P cells had reduced methylation of several histone lysine marks compared with controls. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: NNMT changed several histone methylation marks in this culture model. organism: Human tissue_or_cell_type: Human 769P renal carcinoma cells experimental_model: Immunoblotting of histone methylation in engineered cells 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. Not every histone mark changed; this does not establish global DNA hypomethylation. exposure: NNMT overexpression; 10 or 20 micromolar methionine; GFP and inactive NNMT controls cross_nutrient: true evidence_span: {"source_cache": "artifacts/niacin-consumption-sources/nnmt2013.txt", "locator": "Full text, normalized paragraph 35", "start_char": 19327, "end_char": 21089, "file_sha256": "7d88fd656ba772962185234a9bd021e40a9b83f9156db836f723eba06b68acca", "text_sha256": "5b6ea17ec741ecc064f97de9d83d49809db5e62588ffc1164e6e771fc9fc50c3"} [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
After 24 hours of labeled N1-methylnicotinamide exposure, cancer-cell tracing did not detect conversion to other labeled metabolites.
N1-Methylnicotinamide → N1-Methylnicotinamide turnover 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 33", "start_char": 18035, "end_char": 19275, "file_sha256": "7d88fd656ba772962185234a9bd021e40a9b83f9156db836f723eba06b68acca", "text_sha256": "efcd23e962441fae2b1fb3602db6a6d820ad2d17a511651b3950a2499df2fa02"}
experimental_model
Deuterated metabolite tracing and LC-MS
exposure
Deuterated N1-methylnicotinamide for 24 hours; labeled nicotinamide comparison
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. Non-detection is assay-limited and does not establish absolute irreversibility or whole-body clearance.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Human
plain_language
The methylated product was relatively stable during this cell-culture experiment.
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 817–829
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Deuterated metabolite tracing and LC-MS · source_derived_draft · unverified_draft
### b3-cons-mna-stability After 24 hours of labeled N1-methylnicotinamide exposure, cancer-cell tracing did not detect conversion to other labeled metabolites. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The methylated product was relatively stable during this cell-culture experiment. organism: Human tissue_or_cell_type: Human 769P renal carcinoma cells experimental_model: Deuterated metabolite tracing and LC-MS 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. Non-detection is assay-limited and does not establish absolute irreversibility or whole-body clearance. exposure: Deuterated N1-methylnicotinamide for 24 hours; labeled nicotinamide comparison cross_nutrient: true evidence_span: {"source_cache": "artifacts/niacin-consumption-sources/nnmt2013.txt", "locator": "Full text, normalized paragraph 33", "start_char": 18035, "end_char": 19275, "file_sha256": "7d88fd656ba772962185234a9bd021e40a9b83f9156db836f723eba06b68acca", "text_sha256": "efcd23e962441fae2b1fb3602db6a6d820ad2d17a511651b3950a2499df2fa02"} [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
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
Cryo-EM resolved full-length human NADK as a tetramer with active sites spanning adjacent monomers.
NADK → NADK source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/niacin-redox-sources/nadk-human-2025.fulltext.txt", "locator": "Results", "start_char": 4029, "end_char": 5074, "file_sha256": "72c7b9625e1bf4137d6833adac6ae49fc108f2cd75bb4945c5b04d72a0355f9b", "text_sha256": "e3b82e8f1acea39f7023ee7e6d83f6631d0c00ec23d5f98d96cef0707dcaa34c"}
experimental_model
Full-length NADK purified from HEK293 cells; cryo-EM
exposure
Apo protein structure
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 enzyme operates in a four-subunit assembly.
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 protein
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 845–856
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Full-length NADK purified from HEK293 cells; cryo-EM · source_derived_draft · unverified_draft
### b3-redox-nadk-tetramer Cryo-EM resolved full-length human NADK as a tetramer with active sites spanning adjacent monomers. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The cytosolic enzyme operates in a four-subunit assembly. organism: Homo sapiens tissue_or_cell_type: Purified protein experimental_model: Full-length NADK purified from HEK293 cells; cryo-EM limitations: Scoped experimental observation; no dietary niacin or magnesium deficiency threshold or treatment benefit was tested. exposure: Apo protein structure evidence_span: {"source_cache": "artifacts/niacin-redox-sources/nadk-human-2025.fulltext.txt", "locator": "Results", "start_char": 4029, "end_char": 5074, "file_sha256": "72c7b9625e1bf4137d6833adac6ae49fc108f2cd75bb4945c5b04d72a0355f9b", "text_sha256": "e3b82e8f1acea39f7023ee7e6d83f6631d0c00ec23d5f98d96cef0707dcaa34c"} [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
The recombinant human NADK study did not detect phosphorylation of nicotinic acid adenine dinucleotide (NAAD).
NADK → Nicotinic acid adenine dinucleotide source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/niacin-redox-sources/nadk-human-2001.abstract.txt", "locator": "Indexed abstract, substrate specificity", "start_char": 734, "end_char": 1005, "file_sha256": "98ea2e14dad1649e591f0c6420828328f84a7fe9e083e24b7379d6b680f11958", "text_sha256": "e61bb4892b61f0ed3a4b2eda8bc0131424a7854f7bd670fbd1544936b99c4d88"}
experimental_model
Recombinant human NADK
exposure
NAAD compared with NAD
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
Changing the nicotinamide group changes which nucleotide the kinase can use.
primary_references
[nadk-human-2001] Structural and functional characterization of human NAD kinase. (2001). https://pubmed.ncbi.nlm.nih.gov/11594753/ DOI: 10.1006/bbrc.2001.5735
tissue_or_cell_type
Purified enzyme
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 858–869
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human NADK · source_derived_draft · unverified_draft
### b3-redox-nadk-naad-negative The recombinant human NADK study did not detect phosphorylation of nicotinic acid adenine dinucleotide (NAAD). Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Changing the nicotinamide group changes which nucleotide the kinase can use. organism: Homo sapiens tissue_or_cell_type: Purified enzyme experimental_model: Recombinant human NADK limitations: Scoped experimental observation; no dietary niacin or magnesium deficiency threshold or treatment benefit was tested. exposure: NAAD compared with NAD evidence_span: {"source_cache": "artifacts/niacin-redox-sources/nadk-human-2001.abstract.txt", "locator": "Indexed abstract, substrate specificity", "start_char": 734, "end_char": 1005, "file_sha256": "98ea2e14dad1649e591f0c6420828328f84a7fe9e083e24b7379d6b680f11958", "text_sha256": "e61bb4892b61f0ed3a4b2eda8bc0131424a7854f7bd670fbd1544936b99c4d88"} [nadk-human-2001] Structural and functional characterization of human NAD kinase. (2001). https://pubmed.ncbi.nlm.nih.gov/11594753/ DOI: 10.1006/bbrc.2001.5735
Complete structured claim and evidence
Purified human NADK2 Δ62 converted NAD+ to NADP+ with ATP in MgCl2-containing reactions; TLC also detected ADP formation.
NADK2 Δ62 recombinant construct → NADP+ source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Magnesium is present with ATP during phosphorylation of the niacin-derived dinucleotide; this assay does not quantify effects of dietary magnesium shortage.
evidence_span
[{"source_cache": "artifacts/niacin-redox-sources/nadk2-2012.fulltext.txt", "locator": "Results", "start_char": 8475, "end_char": 9580, "file_sha256": "65209c0b4ea7220bc95afdd182e40910f2445345172956e85552d5c6db649648", "text_sha256": "c86810a1a5342cd4e7ea126e070f28ed3182d81f17ea76c0fbb3833612c0f529"}, {"source_cache": "artifacts/niacin-redox-sources/nadk2-2012.fulltext.txt", "locator": "Methods, NADK activity assay", "start_char": 26694, "end_char": 28732, "file_sha256": "65209c0b4ea7220bc95afdd182e40910f2445345172956e85552d5c6db649648", "text_sha256": "907b651f0c0aae7a31306bdc42264cdfd22fb0e236e7ab8f37900467b0b0ab72"}]
experimental_model
Purified His-tagged Δ62C5orf33/NADK2
exposure
TLC: 5 mM NAD+, 5 mM ATP, 5 mM MgCl2; 37°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 mitochondrial kinase uses a phosphate-transfer reaction to create 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
Purified protein
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 871–883
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified His-tagged Δ62C5orf33/NADK2 · source_derived_draft · unverified_draft
### b3-redox-nadk2-phosphorylation Purified human NADK2 Δ62 converted NAD+ to NADP+ with ATP in MgCl2-containing reactions; TLC also detected ADP formation. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The mitochondrial kinase uses a phosphate-transfer reaction to create NADP+. organism: Homo sapiens tissue_or_cell_type: Purified protein experimental_model: Purified His-tagged Δ62C5orf33/NADK2 limitations: Scoped experimental observation; no dietary niacin or magnesium deficiency threshold or treatment benefit was tested. exposure: TLC: 5 mM NAD+, 5 mM ATP, 5 mM MgCl2; 37°C cross_nutrient: Magnesium is present with ATP during phosphorylation of the niacin-derived dinucleotide; this assay does not quantify effects of dietary magnesium shortage. evidence_span: [{"source_cache": "artifacts/niacin-redox-sources/nadk2-2012.fulltext.txt", "locator": "Results", "start_char": 8475, "end_char": 9580, "file_sha256": "65209c0b4ea7220bc95afdd182e40910f2445345172956e85552d5c6db649648", "text_sha256": "c86810a1a5342cd4e7ea126e070f28ed3182d81f17ea76c0fbb3833612c0f529"}, {"source_cache": "artifacts/niacin-redox-sources/nadk2-2012.fulltext.txt", "locator": "Methods, NADK activity assay", "start_char": 26694, "end_char": 28732, "file_sha256": "65209c0b4ea7220bc95afdd182e40910f2445345172956e85552d5c6db649648", "text_sha256": "907b651f0c0aae7a31306bdc42264cdfd22fb0e236e7ab8f37900467b0b0ab72"}] [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
Purified human NADK2 Δ62 also supported NADP+ formation using inorganic polyphosphate preparations as phosphate donors.
NADK2 Δ62 recombinant construct → Inorganic polyphosphate source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Uses phosphate polymers in a magnesium-containing enzyme assay, not a dietary phosphorus intervention.
evidence_span
{"source_cache": "artifacts/niacin-redox-sources/nadk2-2012.fulltext.txt", "locator": "Results", "start_char": 11596, "end_char": 12294, "file_sha256": "65209c0b4ea7220bc95afdd182e40910f2445345172956e85552d5c6db649648", "text_sha256": "f371b72f3f7104e6b2b1f4f28ec55e04b18b931383b51a3258872db0809a10d9"}
experimental_model
Purified NADK2 Δ62
exposure
Metaphosphate, hexametaphosphate and tetrapolyphosphate tested
limitations
In vitro substrate capacity; physiological flux from polyphosphate in human mitochondria was not established. Monomeric phosphate is not interchangeable with these polymers.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Homo sapiens
plain_language
The recombinant mitochondrial enzyme accepted some polyphosphate preparations in vitro.
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
Purified enzyme
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 885–897
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified NADK2 Δ62 · source_derived_draft · unverified_draft
### b3-redox-nadk2-polyphosphate Purified human NADK2 Δ62 also supported NADP+ formation using inorganic polyphosphate preparations as phosphate donors. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The recombinant mitochondrial enzyme accepted some polyphosphate preparations in vitro. organism: Homo sapiens tissue_or_cell_type: Purified enzyme experimental_model: Purified NADK2 Δ62 limitations: In vitro substrate capacity; physiological flux from polyphosphate in human mitochondria was not established. Monomeric phosphate is not interchangeable with these polymers. exposure: Metaphosphate, hexametaphosphate and tetrapolyphosphate tested cross_nutrient: Uses phosphate polymers in a magnesium-containing enzyme assay, not a dietary phosphorus intervention. evidence_span: {"source_cache": "artifacts/niacin-redox-sources/nadk2-2012.fulltext.txt", "locator": "Results", "start_char": 11596, "end_char": 12294, "file_sha256": "65209c0b4ea7220bc95afdd182e40910f2445345172956e85552d5c6db649648", "text_sha256": "f371b72f3f7104e6b2b1f4f28ec55e04b18b931383b51a3258872db0809a10d9"} [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
The tested NADH kinase activity of purified human NADK2 Δ62 was about 10% of its NAD+ kinase activity.
NADK2 Δ62 recombinant construct → NADH source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/niacin-redox-sources/nadk2-2012.fulltext.txt", "locator": "Results", "start_char": 9582, "end_char": 11594, "file_sha256": "65209c0b4ea7220bc95afdd182e40910f2445345172956e85552d5c6db649648", "text_sha256": "ffd25dd072f6f8f486b11ca632f28acf37e3ef2b0dbd2b20eecf32fce649eaf1"}
experimental_model
Purified NADK2 Δ62
exposure
ATP-dependent NADH versus NAD+ assays
limitations
Relative activity under the reported substrate conditions; not a universal cellular flux ratio.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Homo sapiens
plain_language
NADK2 could phosphorylate NADH in this assay, but favored NAD+.
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
Purified enzyme
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 899–910
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified NADK2 Δ62 · source_derived_draft · unverified_draft
### b3-redox-nadk2-nadh-preference The tested NADH kinase activity of purified human NADK2 Δ62 was about 10% of its NAD+ kinase activity. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: NADK2 could phosphorylate NADH in this assay, but favored NAD+. organism: Homo sapiens tissue_or_cell_type: Purified enzyme experimental_model: Purified NADK2 Δ62 limitations: Relative activity under the reported substrate conditions; not a universal cellular flux ratio. exposure: ATP-dependent NADH versus NAD+ assays evidence_span: {"source_cache": "artifacts/niacin-redox-sources/nadk2-2012.fulltext.txt", "locator": "Results", "start_char": 9582, "end_char": 11594, "file_sha256": "65209c0b4ea7220bc95afdd182e40910f2445345172956e85552d5c6db649648", "text_sha256": "ffd25dd072f6f8f486b11ca632f28acf37e3ef2b0dbd2b20eecf32fce649eaf1"} [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
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
The same short NADK2-knockdown experiment did not detect reduced HEK293A viability, including in the tested menadione condition.
NADK2 → HEK293A cell viability 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; calcein-AM and supporting MTT assays
exposure
Three-day knockdown; viability experiment used 12.5 μM menadione for 20 h
limitations
Null short-term viability result does not exclude longer-term injury or other cell-type responses; ROS and viability challenges used different concentrations.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Homo sapiens
plain_language
The oxidant readout rose without a detected loss of viability over this interval.
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 951–962
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · siRNA; calcein-AM and supporting MTT assays · source_derived_draft · unverified_draft
### b3-redox-nadk2-knockdown-viability-null The same short NADK2-knockdown experiment did not detect reduced HEK293A viability, including in the tested menadione condition. Condition category: machinery_impairment nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The oxidant readout rose without a detected loss of viability over this interval. organism: Homo sapiens tissue_or_cell_type: HEK293A cells experimental_model: siRNA; calcein-AM and supporting MTT assays limitations: Null short-term viability result does not exclude longer-term injury or other cell-type responses; ROS and viability challenges used different concentrations. exposure: Three-day knockdown; viability experiment used 12.5 μM menadione for 20 h 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
Patient fibroblasts bearing a pathogenic NADK2 alteration had reduced mitochondrial NADP(H).
NADK2 loss-of-function genotype → Mitochondrial NADP(H) 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/nadk2-patient-2014.abstract.txt", "locator": "Indexed abstract, genetic and fibroblast results", "start_char": 357, "end_char": 1462, "file_sha256": "0e8ce719f0454f41ce98a5c35f75c88a21f5219f0d9b574cf8a793697f39db5a", "text_sha256": "e468b1beee1be208d337cdf94488aca05296b2dd3fcbba587ca323b8db6d2c96"}
experimental_model
Patient-derived fibroblasts
exposure
Inherited NADK2 alteration
limitations
Single described patient context; mitochondrial NADP(H) shortage arose from kinase machinery impairment, not demonstrated dietary niacin shortage.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Homo sapiens
plain_language
The genetic defect impaired the mitochondrial phosphorylated cofactor pool.
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 964–975
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Patient-derived fibroblasts · source_derived_draft · unverified_draft
### b3-redox-nadk2-patient-pool Patient fibroblasts bearing a pathogenic NADK2 alteration had reduced mitochondrial NADP(H). Condition category: machinery_impairment nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The genetic defect impaired the mitochondrial phosphorylated cofactor pool. organism: Homo sapiens tissue_or_cell_type: Fibroblasts experimental_model: Patient-derived fibroblasts limitations: Single described patient context; mitochondrial NADP(H) shortage arose from kinase machinery impairment, not demonstrated dietary niacin shortage. exposure: Inherited NADK2 alteration evidence_span: {"source_cache": "artifacts/niacin-redox-sources/nadk2-patient-2014.abstract.txt", "locator": "Indexed abstract, genetic and fibroblast results", "start_char": 357, "end_char": 1462, "file_sha256": "0e8ce719f0454f41ce98a5c35f75c88a21f5219f0d9b574cf8a793697f39db5a", "text_sha256": "e468b1beee1be208d337cdf94488aca05296b2dd3fcbba587ca323b8db6d2c96"} [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
Dienoyl-CoA reductase activity was deficient in lysates from the NADK2 patient fibroblasts.
NADK2 loss-of-function genotype → 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, enzyme assay", "start_char": 706, "end_char": 1462, "file_sha256": "0e8ce719f0454f41ce98a5c35f75c88a21f5219f0d9b574cf8a793697f39db5a", "text_sha256": "3e8d0b720e24732ab8f9603138f761f1dc2974876c1f81919cf5ecdae2f71eeb"}
experimental_model
Patient fibroblast lysate enzyme assay
exposure
Inherited NADK2 alteration
limitations
Abstract-backed genetic association plus rescue experiment; not proof that niacin supplementation restores enzyme activity.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Homo sapiens
plain_language
The impaired cofactor machinery was accompanied by loss of a dependent fatty-acid enzyme activity.
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 977–988
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Patient fibroblast lysate enzyme assay · source_derived_draft · unverified_draft
### b3-redox-nadk2-patient-decr Dienoyl-CoA reductase activity was deficient in lysates from the NADK2 patient fibroblasts. Condition category: machinery_impairment nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The impaired cofactor machinery was accompanied by loss of a dependent fatty-acid enzyme activity. organism: Homo sapiens tissue_or_cell_type: Fibroblasts experimental_model: Patient fibroblast lysate enzyme assay limitations: Abstract-backed genetic association plus rescue experiment; not proof that niacin supplementation restores enzyme activity. exposure: Inherited NADK2 alteration evidence_span: {"source_cache": "artifacts/niacin-redox-sources/nadk2-patient-2014.abstract.txt", "locator": "Indexed abstract, enzyme assay", "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
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
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
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
Unlike NAD+, exogenous nicotinamide or NMN did not replenish matrix NAD+ in the isolated-mitochondrial assay.
Nicotinamide → Mitochondrial NAD+ content source_derived_draftungraded
Experimental context and source evidence
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": 19225, "file_sha256": "8348dbfda6d16d576bb64301f0c75f1488e90e33c4a72213b69756bed21d047d", "text_sha256": "121f48fd5cc272acc24a9ca1610c801423a98e3e44f7851e649c8454750e7fb0"}
experimental_model
Isolated mitochondria substrate comparison
exposure
Exogenous NAD+, nicotinamide or NMN
limitations
Does not imply oral NAM/NMN cannot contribute to mitochondrial NAD after extramitochondrial metabolism; this is an isolated-organelle test.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Homo sapiens
plain_language
These precursors were not interchangeable with intact NAD in this uptake experiment.
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 human-cell mitochondria
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 1068–1079
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Isolated mitochondria substrate comparison · source_derived_draft · unverified_draft
### b3-redox-slc25a51-nam-nmn-null Unlike NAD+, exogenous nicotinamide or NMN did not replenish matrix NAD+ in the isolated-mitochondrial assay. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: These precursors were not interchangeable with intact NAD in this uptake experiment. organism: Homo sapiens tissue_or_cell_type: Isolated human-cell mitochondria experimental_model: Isolated mitochondria substrate comparison limitations: Does not imply oral NAM/NMN cannot contribute to mitochondrial NAD after extramitochondrial metabolism; this is an isolated-organelle test. exposure: Exogenous NAD+, nicotinamide or NMN 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": 19225, "file_sha256": "8348dbfda6d16d576bb64301f0c75f1488e90e33c4a72213b69756bed21d047d", "text_sha256": "121f48fd5cc272acc24a9ca1610c801423a98e3e44f7851e649c8454750e7fb0"} [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
Excess NMN or nicotinamide did not compete with NAD+ uptake in the isolated-mitochondrial competition assay.
NMN → Mitochondrial NAD+ uptake source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/niacin-redox-sources/slc25a51-2020.author.txt", "locator": "Publisher PDF, results; page/figure identified by adjacent text", "start_char": 19115, "end_char": 19225, "file_sha256": "8348dbfda6d16d576bb64301f0c75f1488e90e33c4a72213b69756bed21d047d", "text_sha256": "71f08e5c405c67340bfbe5e1d027cebc9c0f37a2e64bdbd4205020f1ee23e005"}
experimental_model
Competition assay with isolated human-cell mitochondria
exposure
Excess precursor alongside NAD+
limitations
Assay-specific negative competition; no assertion that every derivative is excluded from all transporters.
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 precursors did not block the measured NAD import route.
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
Mitochondria
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 1081–1092
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Competition assay with isolated human-cell mitochondria · source_derived_draft · unverified_draft
### b3-redox-slc25a51-precursor-competition-null Excess NMN or nicotinamide did not compete with NAD+ uptake in the isolated-mitochondrial competition assay. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The two precursors did not block the measured NAD import route. organism: Homo sapiens tissue_or_cell_type: Mitochondria experimental_model: Competition assay with isolated human-cell mitochondria limitations: Assay-specific negative competition; no assertion that every derivative is excluded from all transporters. exposure: Excess precursor alongside NAD+ evidence_span: {"source_cache": "artifacts/niacin-redox-sources/slc25a51-2020.author.txt", "locator": "Publisher PDF, results; page/figure identified by adjacent text", "start_char": 19115, "end_char": 19225, "file_sha256": "8348dbfda6d16d576bb64301f0c75f1488e90e33c4a72213b69756bed21d047d", "text_sha256": "71f08e5c405c67340bfbe5e1d027cebc9c0f37a2e64bdbd4205020f1ee23e005"} [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
At both low niacin-equivalent intakes, erythrocyte NAD fell by about 70% in the seven-man feeding study and increased during adequate-intake repletion.
Niacin (vitamin B3) → Erythrocyte NAD content source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
L-Tryptophan (alternative_precursor); Nicotinamide adenine dinucleotide, oxidized (measured_coenzyme)
evidence_span
{"source_cache": "artifacts/niacin-clinical-sources/fu1989.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "ca6d94c101aca84f1e41f35898434f44770ca563c5bff986fe52e33f797b0fbc", "start_char": 0, "end_char": 1340, "text_sha256": "ca6d94c101aca84f1e41f35898434f44770ca563c5bff986fe52e33f797b0fbc"}
experimental_model
Controlled metabolic-unit feeding; seven men, 80 days
exposure
6.1 or 10.1 niacin equivalents/day, followed by adequate/high intakes; repletion with or without 7.8 g/day leucine
limitations
Small controlled male metabolic-unit study. Erythrocytes are not every tissue; historical adequate intake is not a current recommendation. Jacob and Fu reports may describe related participants and are not counted as independent trials.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Homo sapiens
plain_language
With too little niacin and tryptophan, red blood cells lost much of their NAD supply; restoring intake raised it.
primary_references
[nia-clin-fu1989] Biochemical markers for assessment of niacin status in young men: levels of erythrocyte niacin coenzymes and plasma tryptophan. (1989). https://pubmed.ncbi.nlm.nih.gov/2621487/ DOI: 10.1093/jn/119.12.1949
tissue_or_cell_type
Erythrocytes and plasma
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 1107–1119
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Controlled metabolic-unit feeding; seven men, 80 days · source_derived_draft · unverified_draft
### nia-clin-restriction-nad At both low niacin-equivalent intakes, erythrocyte NAD fell by about 70% in the seven-man feeding study and increased during adequate-intake repletion. Condition category: nutrient_deficiency nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: With too little niacin and tryptophan, red blood cells lost much of their NAD supply; restoring intake raised it. organism: Homo sapiens tissue_or_cell_type: Erythrocytes and plasma experimental_model: Controlled metabolic-unit feeding; seven men, 80 days limitations: Small controlled male metabolic-unit study. Erythrocytes are not every tissue; historical adequate intake is not a current recommendation. Jacob and Fu reports may describe related participants and are not counted as independent trials. exposure: 6.1 or 10.1 niacin equivalents/day, followed by adequate/high intakes; repletion with or without 7.8 g/day leucine cross_nutrient: L-Tryptophan (alternative_precursor); Nicotinamide adenine dinucleotide, oxidized (measured_coenzyme) evidence_span: {"source_cache": "artifacts/niacin-clinical-sources/fu1989.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "ca6d94c101aca84f1e41f35898434f44770ca563c5bff986fe52e33f797b0fbc", "start_char": 0, "end_char": 1340, "text_sha256": "ca6d94c101aca84f1e41f35898434f44770ca563c5bff986fe52e33f797b0fbc"} [nia-clin-fu1989] Biochemical markers for assessment of niacin status in young men: levels of erythrocyte niacin coenzymes and plasma tryptophan. (1989). https://pubmed.ncbi.nlm.nih.gov/2621487/ DOI: 10.1093/jn/119.12.1949
Complete structured claim and evidence
Erythrocyte NADP remained relatively unchanged during the low-NE diets that depleted erythrocyte NAD.
Niacin (vitamin B3) → Erythrocyte NADP content source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Oxidized nicotinamide adenine dinucleotide phosphate (measured_coenzyme)
evidence_span
{"source_cache": "artifacts/niacin-clinical-sources/fu1989.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "ca6d94c101aca84f1e41f35898434f44770ca563c5bff986fe52e33f797b0fbc", "start_char": 0, "end_char": 1340, "text_sha256": "ca6d94c101aca84f1e41f35898434f44770ca563c5bff986fe52e33f797b0fbc"}
experimental_model
Controlled metabolic-unit feeding; seven men, 80 days
exposure
6.1 or 10.1 niacin equivalents/day, followed by adequate/high intakes; repletion with or without 7.8 g/day leucine
limitations
Small controlled male metabolic-unit study. Erythrocytes are not every tissue; historical adequate intake is not a current recommendation. Jacob and Fu reports may describe related participants and are not counted as independent trials.
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 coenzyme pools did not fall together; low niacin did not mean equal loss of NAD and NADP.
primary_references
[nia-clin-fu1989] Biochemical markers for assessment of niacin status in young men: levels of erythrocyte niacin coenzymes and plasma tryptophan. (1989). https://pubmed.ncbi.nlm.nih.gov/2621487/ DOI: 10.1093/jn/119.12.1949
tissue_or_cell_type
Erythrocytes and plasma
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 1121–1133
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Controlled metabolic-unit feeding; seven men, 80 days · source_derived_draft · unverified_draft
### nia-clin-restriction-nadp Erythrocyte NADP remained relatively unchanged during the low-NE diets that depleted erythrocyte NAD. Condition category: nutrient_deficiency nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The two coenzyme pools did not fall together; low niacin did not mean equal loss of NAD and NADP. organism: Homo sapiens tissue_or_cell_type: Erythrocytes and plasma experimental_model: Controlled metabolic-unit feeding; seven men, 80 days limitations: Small controlled male metabolic-unit study. Erythrocytes are not every tissue; historical adequate intake is not a current recommendation. Jacob and Fu reports may describe related participants and are not counted as independent trials. exposure: 6.1 or 10.1 niacin equivalents/day, followed by adequate/high intakes; repletion with or without 7.8 g/day leucine cross_nutrient: Oxidized nicotinamide adenine dinucleotide phosphate (measured_coenzyme) evidence_span: {"source_cache": "artifacts/niacin-clinical-sources/fu1989.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "ca6d94c101aca84f1e41f35898434f44770ca563c5bff986fe52e33f797b0fbc", "start_char": 0, "end_char": 1340, "text_sha256": "ca6d94c101aca84f1e41f35898434f44770ca563c5bff986fe52e33f797b0fbc"} [nia-clin-fu1989] Biochemical markers for assessment of niacin status in young men: levels of erythrocyte niacin coenzymes and plasma tryptophan. (1989). https://pubmed.ncbi.nlm.nih.gov/2621487/ DOI: 10.1093/jn/119.12.1949
Complete structured claim and evidence
Adding 7.8 g/day leucine during repletion did not change end-period erythrocyte NAD or NADP or plasma tryptophan in this study.
L-Leucine → Erythrocyte NAD content source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Niacin (vitamin B3) (repleted_nutrient); L-Tryptophan (measured_precursor); Oxidized nicotinamide adenine dinucleotide phosphate (co_measured_pool)
evidence_span
{"source_cache": "artifacts/niacin-clinical-sources/fu1989.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "ca6d94c101aca84f1e41f35898434f44770ca563c5bff986fe52e33f797b0fbc", "start_char": 0, "end_char": 1340, "text_sha256": "ca6d94c101aca84f1e41f35898434f44770ca563c5bff986fe52e33f797b0fbc"}
experimental_model
Controlled metabolic-unit feeding; seven men, 80 days
exposure
6.1 or 10.1 niacin equivalents/day, followed by adequate/high intakes; repletion with or without 7.8 g/day leucine
limitations
Small controlled male metabolic-unit study. Erythrocytes are not every tissue; historical adequate intake is not a current recommendation. Jacob and Fu reports may describe related participants and are not counted as independent trials.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Homo sapiens
plain_language
Extra leucine did not block niacin recovery under this tested diet.
primary_references
[nia-clin-fu1989] Biochemical markers for assessment of niacin status in young men: levels of erythrocyte niacin coenzymes and plasma tryptophan. (1989). https://pubmed.ncbi.nlm.nih.gov/2621487/ DOI: 10.1093/jn/119.12.1949
tissue_or_cell_type
Erythrocytes and plasma
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 1135–1147
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Controlled metabolic-unit feeding; seven men, 80 days · source_derived_draft · unverified_draft
### nia-clin-leucine-repletion Adding 7.8 g/day leucine during repletion did not change end-period erythrocyte NAD or NADP or plasma tryptophan in this study. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Extra leucine did not block niacin recovery under this tested diet. organism: Homo sapiens tissue_or_cell_type: Erythrocytes and plasma experimental_model: Controlled metabolic-unit feeding; seven men, 80 days limitations: Small controlled male metabolic-unit study. Erythrocytes are not every tissue; historical adequate intake is not a current recommendation. Jacob and Fu reports may describe related participants and are not counted as independent trials. exposure: 6.1 or 10.1 niacin equivalents/day, followed by adequate/high intakes; repletion with or without 7.8 g/day leucine cross_nutrient: Niacin (vitamin B3) (repleted_nutrient); L-Tryptophan (measured_precursor); Oxidized nicotinamide adenine dinucleotide phosphate (co_measured_pool) evidence_span: {"source_cache": "artifacts/niacin-clinical-sources/fu1989.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "ca6d94c101aca84f1e41f35898434f44770ca563c5bff986fe52e33f797b0fbc", "start_char": 0, "end_char": 1340, "text_sha256": "ca6d94c101aca84f1e41f35898434f44770ca563c5bff986fe52e33f797b0fbc"} [nia-clin-fu1989] Biochemical markers for assessment of niacin status in young men: levels of erythrocyte niacin coenzymes and plasma tryptophan. (1989). https://pubmed.ncbi.nlm.nih.gov/2621487/ DOI: 10.1093/jn/119.12.1949
Complete structured claim and evidence
Urinary N1-methylnicotinamide below 1.2 mg/day identified the lowest 6.1-NE/day intake in this experiment and was more responsive than 2PY to the 10.1-NE/day diet.
Niacin (vitamin B3) → Urinary N1-methylnicotinamide excretion source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
N1-methylnicotinamide (measured_metabolite)
evidence_span
{"source_cache": "artifacts/niacin-clinical-sources/jacob1989.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "749fc69d8d6cb1ba79a0b17e38e9300611713e3939224ba9ac809cef91c7a64c", "start_char": 0, "end_char": 1463, "text_sha256": "749fc69d8d6cb1ba79a0b17e38e9300611713e3939224ba9ac809cef91c7a64c"}
experimental_model
Controlled metabolic-unit feeding of young men for 11 weeks
exposure
6.1–32 NE/day; oral nicotinamide test doses
limitations
Small controlled male metabolic-unit study. Erythrocytes are not every tissue; historical adequate intake is not a current recommendation. Jacob and Fu reports may describe related participants and are not counted as independent trials. Historical NMN abbreviation means N1-methylnicotinamide, not nicotinamide mononucleotide. Urinary output is not a universal diagnostic cutoff.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Homo sapiens
plain_language
Less niacin intake left less methylated niacin waste in urine; the study threshold belongs to this particular experiment.
primary_references
[nia-clin-jacob1989] Biochemical markers for assessment of niacin status in young men: urinary and blood levels of niacin metabolites. (1989). https://pubmed.ncbi.nlm.nih.gov/2522982/ DOI: 10.1093/jn/119.4.591
tissue_or_cell_type
Urine and plasma
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 1149–1161
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Controlled metabolic-unit feeding of young men for 11 weeks · source_derived_draft · unverified_draft
### nia-clin-urine-mna-restriction Urinary N1-methylnicotinamide below 1.2 mg/day identified the lowest 6.1-NE/day intake in this experiment and was more responsive than 2PY to the 10.1-NE/day diet. Condition category: nutrient_deficiency nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Less niacin intake left less methylated niacin waste in urine; the study threshold belongs to this particular experiment. organism: Homo sapiens tissue_or_cell_type: Urine and plasma experimental_model: Controlled metabolic-unit feeding of young men for 11 weeks limitations: Small controlled male metabolic-unit study. Erythrocytes are not every tissue; historical adequate intake is not a current recommendation. Jacob and Fu reports may describe related participants and are not counted as independent trials. Historical NMN abbreviation means N1-methylnicotinamide, not nicotinamide mononucleotide. Urinary output is not a universal diagnostic cutoff. exposure: 6.1–32 NE/day; oral nicotinamide test doses cross_nutrient: N1-methylnicotinamide (measured_metabolite) evidence_span: {"source_cache": "artifacts/niacin-clinical-sources/jacob1989.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "749fc69d8d6cb1ba79a0b17e38e9300611713e3939224ba9ac809cef91c7a64c", "start_char": 0, "end_char": 1463, "text_sha256": "749fc69d8d6cb1ba79a0b17e38e9300611713e3939224ba9ac809cef91c7a64c"} [nia-clin-jacob1989] Biochemical markers for assessment of niacin status in young men: urinary and blood levels of niacin metabolites. (1989). https://pubmed.ncbi.nlm.nih.gov/2522982/ DOI: 10.1093/jn/119.4.591
Complete structured claim and evidence
Urinary 2PY below 1.2 mg/day tracked the lowest intake; the urinary 2PY-to-methyl-nicotinamide ratio performed less well than individual metabolite outputs and missed the 10.1-NE/day restriction.
Niacin (vitamin B3) → Urinary 2PY excretion source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
N1-methyl-2-pyridone-5-carboxamide (2PY) (measured_metabolite)
evidence_span
{"source_cache": "artifacts/niacin-clinical-sources/jacob1989.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "749fc69d8d6cb1ba79a0b17e38e9300611713e3939224ba9ac809cef91c7a64c", "start_char": 0, "end_char": 1463, "text_sha256": "749fc69d8d6cb1ba79a0b17e38e9300611713e3939224ba9ac809cef91c7a64c"}
experimental_model
Controlled metabolic-unit feeding of young men for 11 weeks
exposure
6.1–32 NE/day; oral nicotinamide test doses
limitations
Small controlled male metabolic-unit study. Erythrocytes are not every tissue; historical adequate intake is not a current recommendation. Jacob and Fu reports may describe related participants and are not counted as independent trials. Historical NMN abbreviation means N1-methylnicotinamide, not nicotinamide mononucleotide. Urinary output is not a universal diagnostic cutoff.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Homo sapiens
plain_language
Individual urine measurements were more informative than assuming their ratio was a better marker.
primary_references
[nia-clin-jacob1989] Biochemical markers for assessment of niacin status in young men: urinary and blood levels of niacin metabolites. (1989). https://pubmed.ncbi.nlm.nih.gov/2522982/ DOI: 10.1093/jn/119.4.591
tissue_or_cell_type
Urine and plasma
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 1163–1175
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Controlled metabolic-unit feeding of young men for 11 weeks · source_derived_draft · unverified_draft
### nia-clin-urine-2py-restriction Urinary 2PY below 1.2 mg/day tracked the lowest intake; the urinary 2PY-to-methyl-nicotinamide ratio performed less well than individual metabolite outputs and missed the 10.1-NE/day restriction. Condition category: nutrient_deficiency nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Individual urine measurements were more informative than assuming their ratio was a better marker. organism: Homo sapiens tissue_or_cell_type: Urine and plasma experimental_model: Controlled metabolic-unit feeding of young men for 11 weeks limitations: Small controlled male metabolic-unit study. Erythrocytes are not every tissue; historical adequate intake is not a current recommendation. Jacob and Fu reports may describe related participants and are not counted as independent trials. Historical NMN abbreviation means N1-methylnicotinamide, not nicotinamide mononucleotide. Urinary output is not a universal diagnostic cutoff. exposure: 6.1–32 NE/day; oral nicotinamide test doses cross_nutrient: N1-methyl-2-pyridone-5-carboxamide (2PY) (measured_metabolite) evidence_span: {"source_cache": "artifacts/niacin-clinical-sources/jacob1989.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "749fc69d8d6cb1ba79a0b17e38e9300611713e3939224ba9ac809cef91c7a64c", "start_char": 0, "end_char": 1463, "text_sha256": "749fc69d8d6cb1ba79a0b17e38e9300611713e3939224ba9ac809cef91c7a64c"} [nia-clin-jacob1989] Biochemical markers for assessment of niacin status in young men: urinary and blood levels of niacin metabolites. (1989). https://pubmed.ncbi.nlm.nih.gov/2522982/ DOI: 10.1093/jn/119.4.591
Complete structured claim and evidence
After the nicotinamide challenge, urinary and plasma methylated-metabolite outputs were similar across ordinary, low-methionine and adequate-methionine periods despite negative nitrogen balance during restriction.
L-Methionine → Methylated niacin metabolite output source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Nicotinamide (challenge_substrate); N1-methylnicotinamide (methylated_product)
evidence_span
{"source_cache": "artifacts/niacin-clinical-sources/swendseid1987.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "9a410f57b23d220c2f97bf589b82b31e6e6f6ca2a7b680c2720e1881a0a71b74", "start_char": 0, "end_char": 1188, "text_sha256": "9a410f57b23d220c2f97bf589b82b31e6e6f6ca2a7b680c2720e1881a0a71b74"}
experimental_model
Sequential controlled diets; five men aged 25–32 years
exposure
10-day ordinary diet; 14 days at 285 mg methionine/day; 7 days at 725 mg/day; end-period nicotinamide challenge 102 micromol/kg
limitations
Methylated metabolite outputs, not all methylation reactions or tissue SAM, were measured. Four participants achieving final-period nitrogen balance contributed the reported comparison. Short exposure, very small study; no inference of unlimited methyl capacity.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Homo sapiens
plain_language
Using methyl groups to dispose of nicotinamide did not automatically exhaust that capacity during this short low-methionine study.
primary_references
[nia-clin-swendseid1987] Methylated niacin derivatives in plasma and urine after an oral dose of nicotinamide given to subjects fed a low-methionine diet. (1987). https://pubmed.ncbi.nlm.nih.gov/2957911/ DOI: 10.1093/ajcn/46.3.496
tissue_or_cell_type
Urine, plasma and nitrogen balance
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 1177–1189
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Sequential controlled diets; five men aged 25–32 years · source_derived_draft · unverified_draft
### nia-clin-methionine-output-preserved After the nicotinamide challenge, urinary and plasma methylated-metabolite outputs were similar across ordinary, low-methionine and adequate-methionine periods despite negative nitrogen balance during restriction. Condition category: nutrient_deficiency nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Using methyl groups to dispose of nicotinamide did not automatically exhaust that capacity during this short low-methionine study. organism: Homo sapiens tissue_or_cell_type: Urine, plasma and nitrogen balance experimental_model: Sequential controlled diets; five men aged 25–32 years limitations: Methylated metabolite outputs, not all methylation reactions or tissue SAM, were measured. Four participants achieving final-period nitrogen balance contributed the reported comparison. Short exposure, very small study; no inference of unlimited methyl capacity. exposure: 10-day ordinary diet; 14 days at 285 mg methionine/day; 7 days at 725 mg/day; end-period nicotinamide challenge 102 micromol/kg cross_nutrient: Nicotinamide (challenge_substrate); N1-methylnicotinamide (methylated_product) evidence_span: {"source_cache": "artifacts/niacin-clinical-sources/swendseid1987.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "9a410f57b23d220c2f97bf589b82b31e6e6f6ca2a7b680c2720e1881a0a71b74", "start_char": 0, "end_char": 1188, "text_sha256": "9a410f57b23d220c2f97bf589b82b31e6e6f6ca2a7b680c2720e1881a0a71b74"} [nia-clin-swendseid1987] Methylated niacin derivatives in plasma and urine after an oral dose of nicotinamide given to subjects fed a low-methionine diet. (1987). https://pubmed.ncbi.nlm.nih.gov/2957911/ DOI: 10.1093/ajcn/46.3.496
Complete structured claim and evidence
The three prolonged corn-diet subjects developed initial pellagra signs between days 50 and 60; lesions differed between individuals, and typical hand dermatitis developed later in two.
Niacin (vitamin B3) → Pellagra clinical lesions source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
L-Tryptophan (co_restricted_precursor)
evidence_span
{"source_cache": "artifacts/niacin-clinical-sources/goldsmith1952.txt", "locator": "Primary full report; exact character range, zero-based and end-exclusive", "file_sha256": "2d4004fb5985f80c8e44909506e1aa05b6eefd838f4c28102beac30fb3092bc5", "start_char": 13468, "end_char": 15488, "text_sha256": "78476c492b7ccdbe08740a06623f5a4856394c368e22b1bfdcdde2bc345e9a36"}
experimental_model
Historical metabolic-ward restriction; seven women, with three prolonged corn-diet cases developing pellagra
exposure
Corn diet about 4.7 mg niacin and 190 mg tryptophan/day; other B-vitamin supplements; 40–135 days depending on subject; subsequent niacinamide or DL-tryptophan
limitations
Very small nonrandomized historical experiment. Diets and exposure durations differed; signs were not universal. Nitrogen balance did not prove niacin sufficiency. This does not establish a modern intake threshold or demonstrate a corn toxin.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Homo sapiens
plain_language
Long enough shortage injured skin and mucosal tissues, but people did not develop the same signs in the same order.
primary_references
[nia-clin-goldsmith1952] Studies of niacin requirement in man. I. Experimental pellagra in subjects on corn diets low in niacin and tryptophan. (1952). https://pubmed.ncbi.nlm.nih.gov/14938430/ DOI: 10.1172/jci102638
tissue_or_cell_type
Skin, oral and intestinal mucosa
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 1191–1203
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Historical metabolic-ward restriction; seven women, with three prolonged corn-diet cases developing pellagra · source_derived_draft · unverified_draft
### nia-clin-pellagra-lesions The three prolonged corn-diet subjects developed initial pellagra signs between days 50 and 60; lesions differed between individuals, and typical hand dermatitis developed later in two. Condition category: nutrient_deficiency nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Long enough shortage injured skin and mucosal tissues, but people did not develop the same signs in the same order. organism: Homo sapiens tissue_or_cell_type: Skin, oral and intestinal mucosa experimental_model: Historical metabolic-ward restriction; seven women, with three prolonged corn-diet cases developing pellagra limitations: Very small nonrandomized historical experiment. Diets and exposure durations differed; signs were not universal. Nitrogen balance did not prove niacin sufficiency. This does not establish a modern intake threshold or demonstrate a corn toxin. exposure: Corn diet about 4.7 mg niacin and 190 mg tryptophan/day; other B-vitamin supplements; 40–135 days depending on subject; subsequent niacinamide or DL-tryptophan cross_nutrient: L-Tryptophan (co_restricted_precursor) evidence_span: {"source_cache": "artifacts/niacin-clinical-sources/goldsmith1952.txt", "locator": "Primary full report; exact character range, zero-based and end-exclusive", "file_sha256": "2d4004fb5985f80c8e44909506e1aa05b6eefd838f4c28102beac30fb3092bc5", "start_char": 13468, "end_char": 15488, "text_sha256": "78476c492b7ccdbe08740a06623f5a4856394c368e22b1bfdcdde2bc345e9a36"} [nia-clin-goldsmith1952] Studies of niacin requirement in man. I. Experimental pellagra in subjects on corn diets low in niacin and tryptophan. (1952). https://pubmed.ncbi.nlm.nih.gov/14938430/ DOI: 10.1172/jci102638
Complete structured claim and evidence
Cheilosis and angular stomatitis occurred during the low-niacin/tryptophan regimen even with approximately 2 mg/day total riboflavin and supplemental pyridoxine; these lesions were not specific evidence of B2 deficiency.
Niacin (vitamin B3) → Niacin-related oral mucosal injury source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Riboflavin (vitamin B2) (supplied_co_nutrient); Pyridoxine (supplied_co_nutrient)
evidence_span
{"source_cache": "artifacts/niacin-clinical-sources/goldsmith1952.txt", "locator": "Primary full report; exact character range, zero-based and end-exclusive", "file_sha256": "2d4004fb5985f80c8e44909506e1aa05b6eefd838f4c28102beac30fb3092bc5", "start_char": 15452, "end_char": 16019, "text_sha256": "66c68d7739e59c3e98f30fe0757f468a7952746f7dfe082138dfa6727fa54bf4"}
experimental_model
Historical metabolic-ward restriction; seven women, with three prolonged corn-diet cases developing pellagra
exposure
Corn diet about 4.7 mg niacin and 190 mg tryptophan/day; other B-vitamin supplements; 40–135 days depending on subject; subsequent niacinamide or DL-tryptophan
limitations
Very small nonrandomized historical experiment. Diets and exposure durations differed; signs were not universal. Nitrogen balance did not prove niacin sufficiency. This does not establish a modern intake threshold or demonstrate a corn toxin.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Homo sapiens
plain_language
A sore mouth can arise from different nutrient problems. The appearance alone did not identify which vitamin was lacking.
primary_references
[nia-clin-goldsmith1952] Studies of niacin requirement in man. I. Experimental pellagra in subjects on corn diets low in niacin and tryptophan. (1952). https://pubmed.ncbi.nlm.nih.gov/14938430/ DOI: 10.1172/jci102638
supplementary_evidence_spans
[{"source_cache": "artifacts/niacin-clinical-sources/goldsmith1952.txt", "start_char": 8901, "end_char": 9290, "file_sha256": "2d4004fb5985f80c8e44909506e1aa05b6eefd838f4c28102beac30fb3092bc5", "text_sha256": "59d1a659822aca95688b5e36bd07b41ea700bfbfdc92b40005acf11bd540b046", "locator": "Methods: supplied B-vitamin quantities"}, {"source_cache": "artifacts/niacin-clinical-sources/goldsmith1952.txt", "start_char": 31540, "end_char": 31811, "file_sha256": "2d4004fb5985f80c8e44909506e1aa05b6eefd838f4c28102beac30fb3092bc5", "text_sha256": "ff226f4114a9dec08a00118aa9df933b8246dc89bcf362b2569c089b511d9d3e", "locator": "Discussion: riboflavin and pyridoxine supplements"}]
tissue_or_cell_type
Skin, oral and intestinal mucosa
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 1205–1218
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Historical metabolic-ward restriction; seven women, with three prolonged corn-diet cases developing pellagra · source_derived_draft · unverified_draft
### nia-clin-pellagra-riboflavin-context Cheilosis and angular stomatitis occurred during the low-niacin/tryptophan regimen even with approximately 2 mg/day total riboflavin and supplemental pyridoxine; these lesions were not specific evidence of B2 deficiency. Condition category: nutrient_deficiency nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A sore mouth can arise from different nutrient problems. The appearance alone did not identify which vitamin was lacking. organism: Homo sapiens tissue_or_cell_type: Skin, oral and intestinal mucosa experimental_model: Historical metabolic-ward restriction; seven women, with three prolonged corn-diet cases developing pellagra limitations: Very small nonrandomized historical experiment. Diets and exposure durations differed; signs were not universal. Nitrogen balance did not prove niacin sufficiency. This does not establish a modern intake threshold or demonstrate a corn toxin. exposure: Corn diet about 4.7 mg niacin and 190 mg tryptophan/day; other B-vitamin supplements; 40–135 days depending on subject; subsequent niacinamide or DL-tryptophan cross_nutrient: Riboflavin (vitamin B2) (supplied_co_nutrient); Pyridoxine (supplied_co_nutrient) evidence_span: {"source_cache": "artifacts/niacin-clinical-sources/goldsmith1952.txt", "locator": "Primary full report; exact character range, zero-based and end-exclusive", "file_sha256": "2d4004fb5985f80c8e44909506e1aa05b6eefd838f4c28102beac30fb3092bc5", "start_char": 15452, "end_char": 16019, "text_sha256": "66c68d7739e59c3e98f30fe0757f468a7952746f7dfe082138dfa6727fa54bf4"} supplementary_evidence_spans: [{"source_cache": "artifacts/niacin-clinical-sources/goldsmith1952.txt", "start_char": 8901, "end_char": 9290, "file_sha256": "2d4004fb5985f80c8e44909506e1aa05b6eefd838f4c28102beac30fb3092bc5", "text_sha256": "59d1a659822aca95688b5e36bd07b41ea700bfbfdc92b40005acf11bd540b046", "locator": "Methods: supplied B-vitamin quantities"}, {"source_cache": "artifacts/niacin-clinical-sources/goldsmith1952.txt", "start_char": 31540, "end_char": 31811, "file_sha256": "2d4004fb5985f80c8e44909506e1aa05b6eefd838f4c28102beac30fb3092bc5", "text_sha256": "ff226f4114a9dec08a00118aa9df933b8246dc89bcf362b2569c089b511d9d3e", "locator": "Discussion: riboflavin and pyridoxine supplements"}] [nia-clin-goldsmith1952] Studies of niacin requirement in man. I. Experimental pellagra in subjects on corn diets low in niacin and tryptophan. (1952). https://pubmed.ncbi.nlm.nih.gov/14938430/ DOI: 10.1172/jci102638
Complete structured claim and evidence
In the two subjects treated with niacinamide, subjective improvement began within 24–48 hours; oral lesions generally healed within a week, while tongue papillae and some skin lesions took longer.
Nicotinamide → Pellagra clinical lesions source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Niacin (vitamin B3) (repleted_nutrient)
evidence_span
{"source_cache": "artifacts/niacin-clinical-sources/goldsmith1952.txt", "locator": "Primary full report; exact character range, zero-based and end-exclusive", "file_sha256": "2d4004fb5985f80c8e44909506e1aa05b6eefd838f4c28102beac30fb3092bc5", "start_char": 16399, "end_char": 17420, "text_sha256": "6b1cded5e0f16d68d3efb6aed24a292273030279ca9d21168b0ca00aa529e0c1"}
experimental_model
Historical metabolic-ward restriction; seven women, with three prolonged corn-diet cases developing pellagra
exposure
Corn diet about 4.7 mg niacin and 190 mg tryptophan/day; other B-vitamin supplements; 40–135 days depending on subject; subsequent niacinamide or DL-tryptophan; Table IV: subject 4 began niacinamide 10 mg three times daily, later 50 mg three times daily; subject 5 received a 50 mg test dose, then 10 mg three times daily, later 25 mg three times daily. Historical study regimens, not individualized treatment instructions.
limitations
Very small nonrandomized historical experiment. Diets and exposure durations differed; signs were not universal. Nitrogen balance did not prove niacin sufficiency. This does not establish a modern intake threshold or demonstrate a corn toxin.
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 missing precursor helped, but different tissues recovered at different speeds.
primary_references
[nia-clin-goldsmith1952] Studies of niacin requirement in man. I. Experimental pellagra in subjects on corn diets low in niacin and tryptophan. (1952). https://pubmed.ncbi.nlm.nih.gov/14938430/ DOI: 10.1172/jci102638
supplementary_evidence_spans
[{"source_cache": "artifacts/niacin-clinical-sources/goldsmith1952.txt", "start_char": 17970, "end_char": 19288, "file_sha256": "2d4004fb5985f80c8e44909506e1aa05b6eefd838f4c28102beac30fb3092bc5", "text_sha256": "238677e2a2fecb4a81c2eed519676bf50bb7d9a3884042ec46934c8a3a570c3a", "locator": "Table IV: subject-specific niacinamide regimens"}]
tissue_or_cell_type
Skin, oral and intestinal mucosa
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 1220–1233
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Historical metabolic-ward restriction; seven women, with three prolonged corn-diet cases developing pellagra · source_derived_draft · unverified_draft
### nia-clin-pellagra-niacinamide-recovery In the two subjects treated with niacinamide, subjective improvement began within 24–48 hours; oral lesions generally healed within a week, while tongue papillae and some skin lesions took longer. Condition category: nutrient_deficiency nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Replacing the missing precursor helped, but different tissues recovered at different speeds. organism: Homo sapiens tissue_or_cell_type: Skin, oral and intestinal mucosa experimental_model: Historical metabolic-ward restriction; seven women, with three prolonged corn-diet cases developing pellagra limitations: Very small nonrandomized historical experiment. Diets and exposure durations differed; signs were not universal. Nitrogen balance did not prove niacin sufficiency. This does not establish a modern intake threshold or demonstrate a corn toxin. exposure: Corn diet about 4.7 mg niacin and 190 mg tryptophan/day; other B-vitamin supplements; 40–135 days depending on subject; subsequent niacinamide or DL-tryptophan; Table IV: subject 4 began niacinamide 10 mg three times daily, later 50 mg three times daily; subject 5 received a 50 mg test dose, then 10 mg three times daily, later 25 mg three times daily. Historical study regimens, not individualized treatment instructions. cross_nutrient: Niacin (vitamin B3) (repleted_nutrient) evidence_span: {"source_cache": "artifacts/niacin-clinical-sources/goldsmith1952.txt", "locator": "Primary full report; exact character range, zero-based and end-exclusive", "file_sha256": "2d4004fb5985f80c8e44909506e1aa05b6eefd838f4c28102beac30fb3092bc5", "start_char": 16399, "end_char": 17420, "text_sha256": "6b1cded5e0f16d68d3efb6aed24a292273030279ca9d21168b0ca00aa529e0c1"} supplementary_evidence_spans: [{"source_cache": "artifacts/niacin-clinical-sources/goldsmith1952.txt", "start_char": 17970, "end_char": 19288, "file_sha256": "2d4004fb5985f80c8e44909506e1aa05b6eefd838f4c28102beac30fb3092bc5", "text_sha256": "238677e2a2fecb4a81c2eed519676bf50bb7d9a3884042ec46934c8a3a570c3a", "locator": "Table IV: subject-specific niacinamide regimens"}] [nia-clin-goldsmith1952] Studies of niacin requirement in man. I. Experimental pellagra in subjects on corn diets low in niacin and tryptophan. (1952). https://pubmed.ncbi.nlm.nih.gov/14938430/ DOI: 10.1172/jci102638
Complete structured claim and evidence
Two patients with homozygous HAAO truncating variants p.D162* or p.W186* belonged to the reported congenital-malformation cohort with reduced circulating NAD.
Biallelic HAAO loss-of-function genotype → Circulating NAD content source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Human 3-hydroxyanthranilate 3,4-dioxygenase / HAAO (affected_enzyme); L-Tryptophan (upstream_precursor); Nicotinamide adenine dinucleotide, oxidized (measured_coenzyme)
evidence_span
{"source_cache": "artifacts/niacin-clinical-sources/shi2017.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "2c5dcc72d338ac41bd47e4363a149abc503859e2760398fed030f02d5891e2bb", "start_char": 0, "end_char": 1874, "text_sha256": "2c5dcc72d338ac41bd47e4363a149abc503859e2760398fed030f02d5891e2bb"}
experimental_model
Four patients from unrelated families; sequencing and circulating metabolites, with parallel enzyme and mouse experiments
exposure
Biallelic HAAO or KYNU loss-of-function variants
limitations
Rare inherited synthesis impairment is distinct from dietary shortage. Prevention with gestational niacin was demonstrated in mice, not as an established prenatal treatment in humans.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Homo sapiens
plain_language
An inherited break in the tryptophan pathway can leave NAD low even when the problem is not simply food intake.
primary_references
[nia-clin-shi2017] NAD Deficiency, Congenital Malformations, and Niacin Supplementation. (2017). https://pubmed.ncbi.nlm.nih.gov/28792876/ DOI: 10.1056/nejmoa1616361
tissue_or_cell_type
Circulation and congenital organ development
trigger_kind
machinery_impairment Imported condition classification; unverified.
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 1235–1247
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Four patients from unrelated families; sequencing and circulating metabolites, with parallel enzyme and mouse experiments · source_derived_draft · unverified_draft
### nia-clin-haao-human-low-nad Two patients with homozygous HAAO truncating variants p.D162* or p.W186* belonged to the reported congenital-malformation cohort with reduced circulating NAD. Condition category: machinery_impairment nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: An inherited break in the tryptophan pathway can leave NAD low even when the problem is not simply food intake. organism: Homo sapiens tissue_or_cell_type: Circulation and congenital organ development experimental_model: Four patients from unrelated families; sequencing and circulating metabolites, with parallel enzyme and mouse experiments limitations: Rare inherited synthesis impairment is distinct from dietary shortage. Prevention with gestational niacin was demonstrated in mice, not as an established prenatal treatment in humans. exposure: Biallelic HAAO or KYNU loss-of-function variants cross_nutrient: Human 3-hydroxyanthranilate 3,4-dioxygenase / HAAO (affected_enzyme); L-Tryptophan (upstream_precursor); Nicotinamide adenine dinucleotide, oxidized (measured_coenzyme) evidence_span: {"source_cache": "artifacts/niacin-clinical-sources/shi2017.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "2c5dcc72d338ac41bd47e4363a149abc503859e2760398fed030f02d5891e2bb", "start_char": 0, "end_char": 1874, "text_sha256": "2c5dcc72d338ac41bd47e4363a149abc503859e2760398fed030f02d5891e2bb"} [nia-clin-shi2017] NAD Deficiency, Congenital Malformations, and Niacin Supplementation. (2017). https://pubmed.ncbi.nlm.nih.gov/28792876/ DOI: 10.1056/nejmoa1616361
Complete structured claim and evidence
The cohort also included homozygous KYNU p.V57Efs*21 and compound-heterozygous p.Y156*/p.F349Kfs*4 patients with reduced circulating NAD and multiple malformations.
Biallelic KYNU loss-of-function genotype → Circulating NAD content source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Human kynureninase / KYNU (affected_enzyme); L-Tryptophan (upstream_precursor); Malformations in congenital NAD deficiency disorder (observed_phenotype)
evidence_span
{"source_cache": "artifacts/niacin-clinical-sources/shi2017.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "2c5dcc72d338ac41bd47e4363a149abc503859e2760398fed030f02d5891e2bb", "start_char": 0, "end_char": 1874, "text_sha256": "2c5dcc72d338ac41bd47e4363a149abc503859e2760398fed030f02d5891e2bb"}
experimental_model
Four patients from unrelated families; sequencing and circulating metabolites, with parallel enzyme and mouse experiments
exposure
Biallelic HAAO or KYNU loss-of-function variants
limitations
Rare inherited synthesis impairment is distinct from dietary shortage. Prevention with gestational niacin was demonstrated in mice, not as an established prenatal treatment in humans.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Homo sapiens
plain_language
KYNU is a second independent point where inherited failure can interrupt NAD production.
primary_references
[nia-clin-shi2017] NAD Deficiency, Congenital Malformations, and Niacin Supplementation. (2017). https://pubmed.ncbi.nlm.nih.gov/28792876/ DOI: 10.1056/nejmoa1616361
tissue_or_cell_type
Circulation and congenital organ development
trigger_kind
machinery_impairment Imported condition classification; unverified.
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 1249–1261
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Four patients from unrelated families; sequencing and circulating metabolites, with parallel enzyme and mouse experiments · source_derived_draft · unverified_draft
### nia-clin-kynu-human-low-nad The cohort also included homozygous KYNU p.V57Efs*21 and compound-heterozygous p.Y156*/p.F349Kfs*4 patients with reduced circulating NAD and multiple malformations. Condition category: machinery_impairment nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: KYNU is a second independent point where inherited failure can interrupt NAD production. organism: Homo sapiens tissue_or_cell_type: Circulation and congenital organ development experimental_model: Four patients from unrelated families; sequencing and circulating metabolites, with parallel enzyme and mouse experiments limitations: Rare inherited synthesis impairment is distinct from dietary shortage. Prevention with gestational niacin was demonstrated in mice, not as an established prenatal treatment in humans. exposure: Biallelic HAAO or KYNU loss-of-function variants cross_nutrient: Human kynureninase / KYNU (affected_enzyme); L-Tryptophan (upstream_precursor); Malformations in congenital NAD deficiency disorder (observed_phenotype) evidence_span: {"source_cache": "artifacts/niacin-clinical-sources/shi2017.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "2c5dcc72d338ac41bd47e4363a149abc503859e2760398fed030f02d5891e2bb", "start_char": 0, "end_char": 1874, "text_sha256": "2c5dcc72d338ac41bd47e4363a149abc503859e2760398fed030f02d5891e2bb"} [nia-clin-shi2017] NAD Deficiency, Congenital Malformations, and Niacin Supplementation. (2017). https://pubmed.ncbi.nlm.nih.gov/28792876/ DOI: 10.1056/nejmoa1616361
Complete structured claim and evidence
In the selected NET cohort, mean plasma tryptophan was 31.8 micromol/L and 45% had urinary N1-methylnicotinamide below the study reference range.
Serotonin-producing neuroendocrine tumor state → Urinary N1-methylnicotinamide excretion source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
cross_nutrient
L-Tryptophan (measured_precursor); N1-methylnicotinamide (measured_metabolite)
evidence_span
{"source_cache": "artifacts/niacin-clinical-sources/bouma2016.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "1c1db5a8c0880ceda2066e1fcf23020ab293689782b99402d9913ff326917497", "start_char": 0, "end_char": 1869, "text_sha256": "1c1db5a8c0880ceda2066e1fcf23020ab293689782b99402d9913ff326917497"}
experimental_model
Retrospective serotonin-producing NET cohort; 42 baseline and 34 paired samples; 133 healthy urine references
exposure
Patients selected for low tryptophan and/or pellagra-associated symptoms; prescribed oral niacin mean 144 mg/day
limitations
No randomized comparator or direct tracer measurement of tryptophan diversion. Biomarker normalization does not establish symptom cure. Indexed abstract does not unambiguously specify the administered chemical form; retain niacin rather than guessing nicotinamide.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Homo sapiens
plain_language
In some serotonin-producing tumor patients, low tryptophan was accompanied by a low niacin marker.
primary_references
[nia-clin-bouma2016] Niacin (Vitamin B3) Supplementation in Patients with Serotonin-Producing Neuroendocrine Tumor. (2016). https://pubmed.ncbi.nlm.nih.gov/26335390/ DOI: 10.1159/000440621
tissue_or_cell_type
Plasma and urine
trigger_kind
biomarker_context Imported condition classification; unverified.
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 1263–1275
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Retrospective serotonin-producing NET cohort; 42 baseline and 34 paired samples; 133 healthy urine references · source_derived_draft · unverified_draft
### nia-clin-net-low-marker In the selected NET cohort, mean plasma tryptophan was 31.8 micromol/L and 45% had urinary N1-methylnicotinamide below the study reference range. Condition category: biomarker_context nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: In some serotonin-producing tumor patients, low tryptophan was accompanied by a low niacin marker. organism: Homo sapiens tissue_or_cell_type: Plasma and urine experimental_model: Retrospective serotonin-producing NET cohort; 42 baseline and 34 paired samples; 133 healthy urine references limitations: No randomized comparator or direct tracer measurement of tryptophan diversion. Biomarker normalization does not establish symptom cure. Indexed abstract does not unambiguously specify the administered chemical form; retain niacin rather than guessing nicotinamide. exposure: Patients selected for low tryptophan and/or pellagra-associated symptoms; prescribed oral niacin mean 144 mg/day cross_nutrient: L-Tryptophan (measured_precursor); N1-methylnicotinamide (measured_metabolite) evidence_span: {"source_cache": "artifacts/niacin-clinical-sources/bouma2016.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "1c1db5a8c0880ceda2066e1fcf23020ab293689782b99402d9913ff326917497", "start_char": 0, "end_char": 1869, "text_sha256": "1c1db5a8c0880ceda2066e1fcf23020ab293689782b99402d9913ff326917497"} [nia-clin-bouma2016] Niacin (Vitamin B3) Supplementation in Patients with Serotonin-Producing Neuroendocrine Tumor. (2016). https://pubmed.ncbi.nlm.nih.gov/26335390/ DOI: 10.1159/000440621
Complete structured claim and evidence
Urinary N1-methylnicotinamide rose into the high-normal range in 86% of initially niacin-deficient patients after supplementation in this retrospective series.
Niacin (vitamin B3) → Urinary N1-methylnicotinamide excretion source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
cross_nutrient
N1-methylnicotinamide (measured_metabolite)
evidence_span
{"source_cache": "artifacts/niacin-clinical-sources/bouma2016.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "1c1db5a8c0880ceda2066e1fcf23020ab293689782b99402d9913ff326917497", "start_char": 0, "end_char": 1869, "text_sha256": "1c1db5a8c0880ceda2066e1fcf23020ab293689782b99402d9913ff326917497"}
experimental_model
Retrospective serotonin-producing NET cohort; 42 baseline and 34 paired samples; 133 healthy urine references
exposure
Patients selected for low tryptophan and/or pellagra-associated symptoms; prescribed oral niacin mean 144 mg/day
limitations
No randomized comparator or direct tracer measurement of tryptophan diversion. Biomarker normalization does not establish symptom cure. Indexed abstract does not unambiguously specify the administered chemical form; retain niacin rather than guessing nicotinamide.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Homo sapiens
plain_language
Supplementation improved the measured niacin-status marker for most deficient patients in this series.
primary_references
[nia-clin-bouma2016] Niacin (Vitamin B3) Supplementation in Patients with Serotonin-Producing Neuroendocrine Tumor. (2016). https://pubmed.ncbi.nlm.nih.gov/26335390/ DOI: 10.1159/000440621
tissue_or_cell_type
Plasma and urine
trigger_kind
biomarker_context Imported condition classification; unverified.
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 1277–1289
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Retrospective serotonin-producing NET cohort; 42 baseline and 34 paired samples; 133 healthy urine references · source_derived_draft · unverified_draft
### nia-clin-net-supplement-marker Urinary N1-methylnicotinamide rose into the high-normal range in 86% of initially niacin-deficient patients after supplementation in this retrospective series. Condition category: biomarker_context nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Supplementation improved the measured niacin-status marker for most deficient patients in this series. organism: Homo sapiens tissue_or_cell_type: Plasma and urine experimental_model: Retrospective serotonin-producing NET cohort; 42 baseline and 34 paired samples; 133 healthy urine references limitations: No randomized comparator or direct tracer measurement of tryptophan diversion. Biomarker normalization does not establish symptom cure. Indexed abstract does not unambiguously specify the administered chemical form; retain niacin rather than guessing nicotinamide. exposure: Patients selected for low tryptophan and/or pellagra-associated symptoms; prescribed oral niacin mean 144 mg/day cross_nutrient: N1-methylnicotinamide (measured_metabolite) evidence_span: {"source_cache": "artifacts/niacin-clinical-sources/bouma2016.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "1c1db5a8c0880ceda2066e1fcf23020ab293689782b99402d9913ff326917497", "start_char": 0, "end_char": 1869, "text_sha256": "1c1db5a8c0880ceda2066e1fcf23020ab293689782b99402d9913ff326917497"} [nia-clin-bouma2016] Niacin (Vitamin B3) Supplementation in Patients with Serotonin-Producing Neuroendocrine Tumor. (2016). https://pubmed.ncbi.nlm.nih.gov/26335390/ DOI: 10.1159/000440621
Complete structured claim and evidence
Nicotinic-acid activation of GPR109A/HCAR2 in the human cell-line assay lowered cAMP through a pertussis-toxin-sensitive pathway.
Human hydroxycarboxylic acid receptor 2 / HCAR2 → Intracellular cyclic AMP content source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Nicotinic acid (agonist); Cyclic adenosine monophosphate (measured_signal)
evidence_span
{"source_cache": "artifacts/niacin-clinical-sources/walters2009.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "2eb822534ed0c8ea9f71ec67288c302e4e375ed9e86cfe70b28f21ae65ffbd4b", "start_char": 0, "end_char": 1537, "text_sha256": "2eb822534ed0c8ea9f71ec67288c302e4e375ed9e86cfe70b28f21ae65ffbd4b"}
experimental_model
Human cell-line nicotinic-acid receptor signaling assay
exposure
Nicotinic-acid stimulation and beta-arrestin perturbation
limitations
Pharmacological receptor signaling, not an essential effect of every B3 precursor. Cell signaling and mouse physiology are distinct arms. Reduced fatty acids or flushing does not establish cardiovascular benefit.
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 can act as a receptor signal as well as a vitamin precursor, switching down a cellular signaling molecule.
primary_references
[nia-clin-walters2009] beta-Arrestin1 mediates nicotinic acid-induced flushing, but not its antilipolytic effect, in mice. (2009). https://pubmed.ncbi.nlm.nih.gov/19349687/ DOI: 10.1172/jci36806
tissue_or_cell_type
Cultured human cells
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 1291–1303
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human cell-line nicotinic-acid receptor signaling assay · source_derived_draft · unverified_draft
### nia-clin-hcar2-camp Nicotinic-acid activation of GPR109A/HCAR2 in the human cell-line assay lowered cAMP through a pertussis-toxin-sensitive pathway. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Nicotinic acid can act as a receptor signal as well as a vitamin precursor, switching down a cellular signaling molecule. organism: Homo sapiens tissue_or_cell_type: Cultured human cells experimental_model: Human cell-line nicotinic-acid receptor signaling assay limitations: Pharmacological receptor signaling, not an essential effect of every B3 precursor. Cell signaling and mouse physiology are distinct arms. Reduced fatty acids or flushing does not establish cardiovascular benefit. exposure: Nicotinic-acid stimulation and beta-arrestin perturbation cross_nutrient: Nicotinic acid (agonist); Cyclic adenosine monophosphate (measured_signal) evidence_span: {"source_cache": "artifacts/niacin-clinical-sources/walters2009.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "2eb822534ed0c8ea9f71ec67288c302e4e375ed9e86cfe70b28f21ae65ffbd4b", "start_char": 0, "end_char": 1537, "text_sha256": "2eb822534ed0c8ea9f71ec67288c302e4e375ed9e86cfe70b28f21ae65ffbd4b"} [nia-clin-walters2009] beta-Arrestin1 mediates nicotinic acid-induced flushing, but not its antilipolytic effect, in mice. (2009). https://pubmed.ncbi.nlm.nih.gov/19349687/ DOI: 10.1172/jci36806
Complete structured claim and evidence
Nicotinic acid promoted beta-arrestin1 association with activated cytosolic phospholipase A2 and beta-arrestin1-dependent phospholipase activation with arachidonate release in the cell assay.
Human beta-arrestin 1 / ARRB1 → Human cytosolic phospholipase A2 alpha / PLA2G4A source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Human hydroxycarboxylic acid receptor 2 / HCAR2 (upstream_receptor); Nicotinic acid (agonist); arachidonic acid (released_substrate)
evidence_span
{"source_cache": "artifacts/niacin-clinical-sources/walters2009.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "2eb822534ed0c8ea9f71ec67288c302e4e375ed9e86cfe70b28f21ae65ffbd4b", "start_char": 0, "end_char": 1537, "text_sha256": "2eb822534ed0c8ea9f71ec67288c302e4e375ed9e86cfe70b28f21ae65ffbd4b"}
experimental_model
Human cell-line nicotinic-acid receptor signaling assay
exposure
Nicotinic-acid stimulation and beta-arrestin perturbation
limitations
Pharmacological receptor signaling, not an essential effect of every B3 precursor. Cell signaling and mouse physiology are distinct arms. Reduced fatty acids or flushing does not establish cardiovascular benefit.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Homo sapiens
plain_language
A separate receptor branch recruits beta-arrestin and releases the fatty-acid material used to make flushing signals.
primary_references
[nia-clin-walters2009] beta-Arrestin1 mediates nicotinic acid-induced flushing, but not its antilipolytic effect, in mice. (2009). https://pubmed.ncbi.nlm.nih.gov/19349687/ DOI: 10.1172/jci36806
tissue_or_cell_type
Cultured human cells
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 1305–1317
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human cell-line nicotinic-acid receptor signaling assay · source_derived_draft · unverified_draft
### nia-clin-arrb1-pla2 Nicotinic acid promoted beta-arrestin1 association with activated cytosolic phospholipase A2 and beta-arrestin1-dependent phospholipase activation with arachidonate release in the cell assay. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A separate receptor branch recruits beta-arrestin and releases the fatty-acid material used to make flushing signals. organism: Homo sapiens tissue_or_cell_type: Cultured human cells experimental_model: Human cell-line nicotinic-acid receptor signaling assay limitations: Pharmacological receptor signaling, not an essential effect of every B3 precursor. Cell signaling and mouse physiology are distinct arms. Reduced fatty acids or flushing does not establish cardiovascular benefit. exposure: Nicotinic-acid stimulation and beta-arrestin perturbation cross_nutrient: Human hydroxycarboxylic acid receptor 2 / HCAR2 (upstream_receptor); Nicotinic acid (agonist); arachidonic acid (released_substrate) evidence_span: {"source_cache": "artifacts/niacin-clinical-sources/walters2009.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "2eb822534ed0c8ea9f71ec67288c302e4e375ed9e86cfe70b28f21ae65ffbd4b", "start_char": 0, "end_char": 1537, "text_sha256": "2eb822534ed0c8ea9f71ec67288c302e4e375ed9e86cfe70b28f21ae65ffbd4b"} [nia-clin-walters2009] beta-Arrestin1 mediates nicotinic acid-induced flushing, but not its antilipolytic effect, in mice. (2009). https://pubmed.ncbi.nlm.nih.gov/19349687/ DOI: 10.1172/jci36806
Complete structured claim and evidence
Arrb1-null mice had less nicotinic-acid-induced flushing while retaining a serum free-fatty-acid response similar to wild-type mice.
Mouse Arrb1 knockout genotype → Nicotinic-acid-induced cutaneous flushing source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Nicotinic acid (administered_agonist); Plasma free fatty acid concentration (preserved_separate_endpoint)
evidence_span
{"source_cache": "artifacts/niacin-clinical-sources/walters2009.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "2eb822534ed0c8ea9f71ec67288c302e4e375ed9e86cfe70b28f21ae65ffbd4b", "start_char": 0, "end_char": 1537, "text_sha256": "2eb822534ed0c8ea9f71ec67288c302e4e375ed9e86cfe70b28f21ae65ffbd4b"}
experimental_model
Human cell-line receptor signaling and separate Arrb1-null mouse physiology
exposure
Nicotinic-acid stimulation and beta-arrestin perturbation
limitations
Pharmacological receptor signaling, not an essential effect of every B3 precursor. Cell signaling and mouse physiology are distinct arms. Reduced fatty acids or flushing does not establish cardiovascular benefit.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Mus musculus
plain_language
The flushing and fatty-acid responses could be separated in mice; one is not a reliable measure of the other.
primary_references
[nia-clin-walters2009] beta-Arrestin1 mediates nicotinic acid-induced flushing, but not its antilipolytic effect, in mice. (2009). https://pubmed.ncbi.nlm.nih.gov/19349687/ DOI: 10.1172/jci36806
tissue_or_cell_type
Engineered cells; mouse skin and serum
trigger_kind
machinery_impairment Imported condition classification; unverified.
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 1319–1331
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human cell-line receptor signaling and separate Arrb1-null mouse physiology · source_derived_draft · unverified_draft
### nia-clin-arrb1-mouse-flush Arrb1-null mice had less nicotinic-acid-induced flushing while retaining a serum free-fatty-acid response similar to wild-type mice. Condition category: machinery_impairment nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The flushing and fatty-acid responses could be separated in mice; one is not a reliable measure of the other. organism: Mus musculus tissue_or_cell_type: Engineered cells; mouse skin and serum experimental_model: Human cell-line receptor signaling and separate Arrb1-null mouse physiology limitations: Pharmacological receptor signaling, not an essential effect of every B3 precursor. Cell signaling and mouse physiology are distinct arms. Reduced fatty acids or flushing does not establish cardiovascular benefit. exposure: Nicotinic-acid stimulation and beta-arrestin perturbation cross_nutrient: Nicotinic acid (administered_agonist); Plasma free fatty acid concentration (preserved_separate_endpoint) evidence_span: {"source_cache": "artifacts/niacin-clinical-sources/walters2009.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "2eb822534ed0c8ea9f71ec67288c302e4e375ed9e86cfe70b28f21ae65ffbd4b", "start_char": 0, "end_char": 1537, "text_sha256": "2eb822534ed0c8ea9f71ec67288c302e4e375ed9e86cfe70b28f21ae65ffbd4b"} [nia-clin-walters2009] beta-Arrestin1 mediates nicotinic acid-induced flushing, but not its antilipolytic effect, in mice. (2009). https://pubmed.ncbi.nlm.nih.gov/19349687/ DOI: 10.1172/jci36806
Complete structured claim and evidence
PUMA-G-deficient mice did not flush after nicotinic acid; transplantation of wild-type bone marrow restored this response.
Mouse Hcar2 knockout genotype → Nicotinic-acid-induced cutaneous flushing source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Nicotinic acid (agonist); Mouse Hcar2 / PUMA-G receptor (affected_receptor)
evidence_span
{"source_cache": "artifacts/niacin-clinical-sources/benyo2005.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "21dedb52cbd8fccaf810dabec7837e471525e0a5462827b21437d2f7b30c44a2", "start_char": 0, "end_char": 1388, "text_sha256": "21dedb52cbd8fccaf810dabec7837e471525e0a5462827b21437d2f7b30c44a2"}
experimental_model
PUMA-G/Hcar2 and prostaglandin-pathway mouse knockout experiments with bone-marrow transplantation
exposure
Nicotinic acid; receptor or cyclooxygenase deletion; wild-type bone-marrow rescue
limitations
Mouse pharmacological flushing experiment. HCAR2 historically GPR109A/HM74A in humans; mouse receptor PUMA-G. The location of the responsible immune cells was inferred, not every human flush directly measured.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Mus musculus
plain_language
The mouse flushing signal required the receptor in a population supplied by bone marrow.
primary_references
[nia-clin-benyo2005] GPR109A (PUMA-G/HM74A) mediates nicotinic acid-induced flushing. (2005). https://pubmed.ncbi.nlm.nih.gov/16322797/ DOI: 10.1172/jci23626
tissue_or_cell_type
Skin vasculature and hematopoietic cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 1333–1345
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · PUMA-G/Hcar2 and prostaglandin-pathway mouse knockout experiments with bone-marrow transplantation · source_derived_draft · unverified_draft
### nia-clin-hcar2-mouse-flush PUMA-G-deficient mice did not flush after nicotinic acid; transplantation of wild-type bone marrow restored this response. Condition category: machinery_impairment nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The mouse flushing signal required the receptor in a population supplied by bone marrow. organism: Mus musculus tissue_or_cell_type: Skin vasculature and hematopoietic cells experimental_model: PUMA-G/Hcar2 and prostaglandin-pathway mouse knockout experiments with bone-marrow transplantation limitations: Mouse pharmacological flushing experiment. HCAR2 historically GPR109A/HM74A in humans; mouse receptor PUMA-G. The location of the responsible immune cells was inferred, not every human flush directly measured. exposure: Nicotinic acid; receptor or cyclooxygenase deletion; wild-type bone-marrow rescue cross_nutrient: Nicotinic acid (agonist); Mouse Hcar2 / PUMA-G receptor (affected_receptor) evidence_span: {"source_cache": "artifacts/niacin-clinical-sources/benyo2005.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "21dedb52cbd8fccaf810dabec7837e471525e0a5462827b21437d2f7b30c44a2", "start_char": 0, "end_char": 1388, "text_sha256": "21dedb52cbd8fccaf810dabec7837e471525e0a5462827b21437d2f7b30c44a2"} [nia-clin-benyo2005] GPR109A (PUMA-G/HM74A) mediates nicotinic acid-induced flushing. (2005). https://pubmed.ncbi.nlm.nih.gov/16322797/ DOI: 10.1172/jci23626
Complete structured claim and evidence
Nicotinic-acid flushing was absent in cyclooxygenase-1-deficient mice and reduced in mice lacking the tested PGD2 or PGE2 receptors, supporting prostaglandin involvement.
Prostaglandin D2 → Nicotinic-acid-induced cutaneous flushing source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Prostaglandin E2 (additional_signal); Nicotinic acid (trigger)
evidence_span
{"source_cache": "artifacts/niacin-clinical-sources/benyo2005.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "21dedb52cbd8fccaf810dabec7837e471525e0a5462827b21437d2f7b30c44a2", "start_char": 0, "end_char": 1388, "text_sha256": "21dedb52cbd8fccaf810dabec7837e471525e0a5462827b21437d2f7b30c44a2"}
experimental_model
PUMA-G/Hcar2 and prostaglandin-pathway mouse knockout experiments with bone-marrow transplantation
exposure
Nicotinic acid; receptor or cyclooxygenase deletion; wild-type bone-marrow rescue
limitations
Mouse pharmacological flushing experiment. HCAR2 historically GPR109A/HM74A in humans; mouse receptor PUMA-G. The location of the responsible immune cells was inferred, not every human flush directly measured.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Mus musculus
plain_language
Nicotinic acid triggers prostaglandin signals that widen skin vessels in this mouse model.
primary_references
[nia-clin-benyo2005] GPR109A (PUMA-G/HM74A) mediates nicotinic acid-induced flushing. (2005). https://pubmed.ncbi.nlm.nih.gov/16322797/ DOI: 10.1172/jci23626
tissue_or_cell_type
Skin vasculature and hematopoietic cells
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 1347–1359
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · PUMA-G/Hcar2 and prostaglandin-pathway mouse knockout experiments with bone-marrow transplantation · source_derived_draft · unverified_draft
### nia-clin-prostaglandin-flush Nicotinic-acid flushing was absent in cyclooxygenase-1-deficient mice and reduced in mice lacking the tested PGD2 or PGE2 receptors, supporting prostaglandin involvement. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Nicotinic acid triggers prostaglandin signals that widen skin vessels in this mouse model. organism: Mus musculus tissue_or_cell_type: Skin vasculature and hematopoietic cells experimental_model: PUMA-G/Hcar2 and prostaglandin-pathway mouse knockout experiments with bone-marrow transplantation limitations: Mouse pharmacological flushing experiment. HCAR2 historically GPR109A/HM74A in humans; mouse receptor PUMA-G. The location of the responsible immune cells was inferred, not every human flush directly measured. exposure: Nicotinic acid; receptor or cyclooxygenase deletion; wild-type bone-marrow rescue cross_nutrient: Prostaglandin E2 (additional_signal); Nicotinic acid (trigger) evidence_span: {"source_cache": "artifacts/niacin-clinical-sources/benyo2005.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "21dedb52cbd8fccaf810dabec7837e471525e0a5462827b21437d2f7b30c44a2", "start_char": 0, "end_char": 1388, "text_sha256": "21dedb52cbd8fccaf810dabec7837e471525e0a5462827b21437d2f7b30c44a2"} [nia-clin-benyo2005] GPR109A (PUMA-G/HM74A) mediates nicotinic acid-induced flushing. (2005). https://pubmed.ncbi.nlm.nih.gov/16322797/ DOI: 10.1172/jci23626
Complete structured claim and evidence
In healthy men and women, the DP1 antagonist MK-0524 reduced nicotinic-acid-induced flushing symptoms and the rise in skin perfusion.
Laropiprant / MK-0524 → Cutaneous perfusion source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Human prostaglandin D2 receptor 1 / PTGDR (antagonized_receptor); Prostaglandin D2 (receptor_ligand); Nicotinic acid (trigger)
evidence_span
{"source_cache": "artifacts/niacin-clinical-sources/cheng2006.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "3484f8e99487e3991c36a62fd4cdf3972f81de279a50f040f82356da18d74a24", "start_char": 0, "end_char": 1708, "text_sha256": "3484f8e99487e3991c36a62fd4cdf3972f81de279a50f040f82356da18d74a24"}
experimental_model
Mouse receptor pharmacology with separate healthy-human flushing study
exposure
Nicotinic acid with or without the DP1 antagonist MK-0524
limitations
Human reduction in flushing is separate from lipid outcomes. Dose details not present in indexed abstract. Antagonism did not prove all flushing depends on one prostaglandin receptor; male knockout mice retained an aspirin-sensitive component.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Homo sapiens
plain_language
Blocking a prostaglandin receptor reduced the flush in people; that result alone says nothing about long-term cardiovascular outcomes.
primary_references
[nia-clin-cheng2006] Antagonism of the prostaglandin D2 receptor 1 suppresses nicotinic acid-induced vasodilation in mice and humans. (2006). https://pubmed.ncbi.nlm.nih.gov/16617107/ DOI: 10.1073/pnas.0601574103
tissue_or_cell_type
Skin perfusion
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 1361–1373
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse receptor pharmacology with separate healthy-human flushing study · source_derived_draft · unverified_draft
### nia-clin-dp1-human-flush In healthy men and women, the DP1 antagonist MK-0524 reduced nicotinic-acid-induced flushing symptoms and the rise in skin perfusion. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Blocking a prostaglandin receptor reduced the flush in people; that result alone says nothing about long-term cardiovascular outcomes. organism: Homo sapiens tissue_or_cell_type: Skin perfusion experimental_model: Mouse receptor pharmacology with separate healthy-human flushing study limitations: Human reduction in flushing is separate from lipid outcomes. Dose details not present in indexed abstract. Antagonism did not prove all flushing depends on one prostaglandin receptor; male knockout mice retained an aspirin-sensitive component. exposure: Nicotinic acid with or without the DP1 antagonist MK-0524 cross_nutrient: Human prostaglandin D2 receptor 1 / PTGDR (antagonized_receptor); Prostaglandin D2 (receptor_ligand); Nicotinic acid (trigger) evidence_span: {"source_cache": "artifacts/niacin-clinical-sources/cheng2006.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "3484f8e99487e3991c36a62fd4cdf3972f81de279a50f040f82356da18d74a24", "start_char": 0, "end_char": 1708, "text_sha256": "3484f8e99487e3991c36a62fd4cdf3972f81de279a50f040f82356da18d74a24"} [nia-clin-cheng2006] Antagonism of the prostaglandin D2 receptor 1 suppresses nicotinic acid-induced vasodilation in mice and humans. (2006). https://pubmed.ncbi.nlm.nih.gov/16617107/ DOI: 10.1073/pnas.0601574103
Complete structured claim and evidence
In AIM-HIGH, median HDL cholesterol in the niacin arm rose from 35 to 42 mg/dL at two years, with concurrent triglyceride and LDL reductions.
Nicotinic acid → HDL cholesterol concentration source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Niacin precursor form and the measured endpoint are separate graph entities.
evidence_span
{"source_cache": "artifacts/niacin-clinical-sources/aimhigh2011.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "eefcc0d7eed5694eb9d1861a06fc5a256986753607c2095996304fd0de25f3aa", "start_char": 0, "end_char": 2340, "text_sha256": "eefcc0d7eed5694eb9d1861a06fc5a256986753607c2095996304fd0de25f3aa"}
experimental_model
AIM-HIGH randomized trial; 3,414 patients with established cardiovascular disease on intensive statin therapy
exposure
Extended-release nicotinic acid 1,500–2,000 mg/day versus placebo; mean 3-year follow-up
limitations
Pharmacological dosing added to statin therapy. Lipid changes are not equivalent to clinical benefit. Trial stopped for lack of efficacy; no inference about treating 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
The drug changed blood lipids in the intended direction.
primary_references
[nia-clin-aimhigh2011] Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. (2011). https://pubmed.ncbi.nlm.nih.gov/22085343/ DOI: 10.1056/nejmoa1107579
tissue_or_cell_type
Circulating lipids and cardiovascular outcomes
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 1375–1387
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · AIM-HIGH randomized trial; 3,414 patients with established cardiovascular disease on intensive statin therapy · source_derived_draft · unverified_draft
### nia-clin-aimhigh-hdl In AIM-HIGH, median HDL cholesterol in the niacin arm rose from 35 to 42 mg/dL at two years, with concurrent triglyceride and LDL reductions. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The drug changed blood lipids in the intended direction. organism: Homo sapiens tissue_or_cell_type: Circulating lipids and cardiovascular outcomes experimental_model: AIM-HIGH randomized trial; 3,414 patients with established cardiovascular disease on intensive statin therapy limitations: Pharmacological dosing added to statin therapy. Lipid changes are not equivalent to clinical benefit. Trial stopped for lack of efficacy; no inference about treating dietary niacin deficiency. exposure: Extended-release nicotinic acid 1,500–2,000 mg/day versus placebo; mean 3-year follow-up cross_nutrient: Niacin precursor form and the measured endpoint are separate graph entities. evidence_span: {"source_cache": "artifacts/niacin-clinical-sources/aimhigh2011.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "eefcc0d7eed5694eb9d1861a06fc5a256986753607c2095996304fd0de25f3aa", "start_char": 0, "end_char": 2340, "text_sha256": "eefcc0d7eed5694eb9d1861a06fc5a256986753607c2095996304fd0de25f3aa"} [nia-clin-aimhigh2011] Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. (2011). https://pubmed.ncbi.nlm.nih.gov/22085343/ DOI: 10.1056/nejmoa1107579
Complete structured claim and evidence
The AIM-HIGH composite endpoint occurred in 16.4% versus 16.2% of niacin and placebo participants: hazard ratio 1.02, 95% CI 0.87–1.21.
Nicotinic acid → Major cardiovascular event incidence source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Niacin precursor form and the measured endpoint are separate graph entities.
evidence_span
{"source_cache": "artifacts/niacin-clinical-sources/aimhigh2011.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "eefcc0d7eed5694eb9d1861a06fc5a256986753607c2095996304fd0de25f3aa", "start_char": 0, "end_char": 2340, "text_sha256": "eefcc0d7eed5694eb9d1861a06fc5a256986753607c2095996304fd0de25f3aa"}
experimental_model
AIM-HIGH randomized trial; 3,414 patients with established cardiovascular disease on intensive statin therapy
exposure
Extended-release nicotinic acid 1,500–2,000 mg/day versus placebo; mean 3-year follow-up
limitations
Pharmacological dosing added to statin therapy. Lipid changes are not equivalent to clinical benefit. Trial stopped for lack of efficacy; no inference about treating 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
Improved lipid numbers did not translate into fewer trial cardiovascular events in these statin-treated patients.
primary_references
[nia-clin-aimhigh2011] Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. (2011). https://pubmed.ncbi.nlm.nih.gov/22085343/ DOI: 10.1056/nejmoa1107579
tissue_or_cell_type
Circulating lipids and cardiovascular outcomes
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 1389–1401
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · AIM-HIGH randomized trial; 3,414 patients with established cardiovascular disease on intensive statin therapy · source_derived_draft · unverified_draft
### nia-clin-aimhigh-events The AIM-HIGH composite endpoint occurred in 16.4% versus 16.2% of niacin and placebo participants: hazard ratio 1.02, 95% CI 0.87–1.21. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Improved lipid numbers did not translate into fewer trial cardiovascular events in these statin-treated patients. organism: Homo sapiens tissue_or_cell_type: Circulating lipids and cardiovascular outcomes experimental_model: AIM-HIGH randomized trial; 3,414 patients with established cardiovascular disease on intensive statin therapy limitations: Pharmacological dosing added to statin therapy. Lipid changes are not equivalent to clinical benefit. Trial stopped for lack of efficacy; no inference about treating dietary niacin deficiency. exposure: Extended-release nicotinic acid 1,500–2,000 mg/day versus placebo; mean 3-year follow-up cross_nutrient: Niacin precursor form and the measured endpoint are separate graph entities. evidence_span: {"source_cache": "artifacts/niacin-clinical-sources/aimhigh2011.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "eefcc0d7eed5694eb9d1861a06fc5a256986753607c2095996304fd0de25f3aa", "start_char": 0, "end_char": 2340, "text_sha256": "eefcc0d7eed5694eb9d1861a06fc5a256986753607c2095996304fd0de25f3aa"} [nia-clin-aimhigh2011] Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. (2011). https://pubmed.ncbi.nlm.nih.gov/22085343/ DOI: 10.1056/nejmoa1107579
Complete structured claim and evidence
Niacin–laropiprant produced major vascular-event rates of 13.2% versus 13.7% with placebo: rate ratio 0.96, 95% CI 0.90–1.03, without a significant benefit.
Nicotinic acid → Major cardiovascular event incidence source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Laropiprant / MK-0524 (coadministered_drug)
evidence_span
{"source_cache": "artifacts/niacin-clinical-sources/hps2014.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "9f12db5e258418187e65c3b921cffd01bf3cc0f400d3caa19cb4005c5e6f4f05", "start_char": 0, "end_char": 2717, "text_sha256": "9f12db5e258418187e65c3b921cffd01bf3cc0f400d3caa19cb4005c5e6f4f05"}
experimental_model
HPS2-THRIVE randomized trial; 25,673 adults with vascular disease on statin-based therapy
exposure
Extended-release nicotinic acid 2 g plus laropiprant 40 mg daily; median 3.9 years
limitations
Combination regimen; observed harm cannot all be assigned to nicotinic acid alone. Run-in selected participants able to tolerate initial therapy. Outcomes do not address deficiency replacement.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Homo sapiens
plain_language
This large trial also found no clear event benefit when the combination was added to statin treatment.
primary_references
[nia-clin-hps2014] Effects of extended-release niacin with laropiprant in high-risk patients. (2014). https://pubmed.ncbi.nlm.nih.gov/25014686/ DOI: 10.1056/nejmoa1300955
tissue_or_cell_type
Major vascular events and adverse events
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 1403–1415
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · HPS2-THRIVE randomized trial; 25,673 adults with vascular disease on statin-based therapy · source_derived_draft · unverified_draft
### nia-clin-hps-events Niacin–laropiprant produced major vascular-event rates of 13.2% versus 13.7% with placebo: rate ratio 0.96, 95% CI 0.90–1.03, without a significant benefit. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: This large trial also found no clear event benefit when the combination was added to statin treatment. organism: Homo sapiens tissue_or_cell_type: Major vascular events and adverse events experimental_model: HPS2-THRIVE randomized trial; 25,673 adults with vascular disease on statin-based therapy limitations: Combination regimen; observed harm cannot all be assigned to nicotinic acid alone. Run-in selected participants able to tolerate initial therapy. Outcomes do not address deficiency replacement. exposure: Extended-release nicotinic acid 2 g plus laropiprant 40 mg daily; median 3.9 years cross_nutrient: Laropiprant / MK-0524 (coadministered_drug) evidence_span: {"source_cache": "artifacts/niacin-clinical-sources/hps2014.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "9f12db5e258418187e65c3b921cffd01bf3cc0f400d3caa19cb4005c5e6f4f05", "start_char": 0, "end_char": 2717, "text_sha256": "9f12db5e258418187e65c3b921cffd01bf3cc0f400d3caa19cb4005c5e6f4f05"} [nia-clin-hps2014] Effects of extended-release niacin with laropiprant in high-risk patients. (2014). https://pubmed.ncbi.nlm.nih.gov/25014686/ DOI: 10.1056/nejmoa1300955
Complete structured claim and evidence
Niacin–laropiprant increased serious diabetes-control disturbances by 3.7 percentage points and new diabetes diagnoses by 1.3 points; gastrointestinal, musculoskeletal, skin, infection and bleeding serious adverse events also increased.
Nicotinic acid → Serious glycemic adverse-event incidence source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Laropiprant / MK-0524 (coadministered_drug)
evidence_span
{"source_cache": "artifacts/niacin-clinical-sources/hps2014.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "9f12db5e258418187e65c3b921cffd01bf3cc0f400d3caa19cb4005c5e6f4f05", "start_char": 0, "end_char": 2717, "text_sha256": "9f12db5e258418187e65c3b921cffd01bf3cc0f400d3caa19cb4005c5e6f4f05"}
experimental_model
HPS2-THRIVE randomized trial; 25,673 adults with vascular disease on statin-based therapy
exposure
Extended-release nicotinic acid 2 g plus laropiprant 40 mg daily; median 3.9 years
limitations
Combination regimen; observed harm cannot all be assigned to nicotinic acid alone. Run-in selected participants able to tolerate initial therapy. Outcomes do not address deficiency replacement.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Homo sapiens
plain_language
The combination had measurable harms as well as lipid effects.
primary_references
[nia-clin-hps2014] Effects of extended-release niacin with laropiprant in high-risk patients. (2014). https://pubmed.ncbi.nlm.nih.gov/25014686/ DOI: 10.1056/nejmoa1300955
tissue_or_cell_type
Major vascular events and adverse events
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 1417–1429
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · HPS2-THRIVE randomized trial; 25,673 adults with vascular disease on statin-based therapy · source_derived_draft · unverified_draft
### nia-clin-hps-glycemic-harm Niacin–laropiprant increased serious diabetes-control disturbances by 3.7 percentage points and new diabetes diagnoses by 1.3 points; gastrointestinal, musculoskeletal, skin, infection and bleeding serious adverse events also increased. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The combination had measurable harms as well as lipid effects. organism: Homo sapiens tissue_or_cell_type: Major vascular events and adverse events experimental_model: HPS2-THRIVE randomized trial; 25,673 adults with vascular disease on statin-based therapy limitations: Combination regimen; observed harm cannot all be assigned to nicotinic acid alone. Run-in selected participants able to tolerate initial therapy. Outcomes do not address deficiency replacement. exposure: Extended-release nicotinic acid 2 g plus laropiprant 40 mg daily; median 3.9 years cross_nutrient: Laropiprant / MK-0524 (coadministered_drug) evidence_span: {"source_cache": "artifacts/niacin-clinical-sources/hps2014.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "9f12db5e258418187e65c3b921cffd01bf3cc0f400d3caa19cb4005c5e6f4f05", "start_char": 0, "end_char": 2717, "text_sha256": "9f12db5e258418187e65c3b921cffd01bf3cc0f400d3caa19cb4005c5e6f4f05"} [nia-clin-hps2014] Effects of extended-release niacin with laropiprant in high-risk patients. (2014). https://pubmed.ncbi.nlm.nih.gov/25014686/ DOI: 10.1056/nejmoa1300955
Complete structured claim and evidence
During ONTRAC treatment, new nonmelanoma skin cancers were 23% lower with nicotinamide than placebo (95% CI 4–38%); there was no evidence of benefit after discontinuation.
Nicotinamide → New keratinocyte skin cancer incidence source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Niacin precursor form and the measured endpoint are separate graph entities.
evidence_span
{"source_cache": "artifacts/niacin-clinical-sources/chen2015.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "7a305aa1d363f375f8cb640b5ddc5f77517f0229a6041558e392d7a07e198aa8", "start_char": 0, "end_char": 2368, "text_sha256": "7a305aa1d363f375f8cb640b5ddc5f77517f0229a6041558e392d7a07e198aa8"}
experimental_model
ONTRAC double-blind randomized trial; 386 high-risk participants with at least two recent nonmelanoma skin cancers
exposure
Nicotinamide 500 mg twice daily for 12 months; observation for a further six months
limitations
Selected high-risk population; this is pharmacological prevention, not proof of deficiency. Combined endpoint differs from subtype effects. Results do not establish efficacy in every population or after treatment stops.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Homo sapiens
plain_language
Nicotinamide reduced new skin cancers during treatment in this selected high-risk group; protection was not shown to persist after stopping.
primary_references
[nia-clin-chen2015] A Phase 3 Randomized Trial of Nicotinamide for Skin-Cancer Chemoprevention. (2015). https://pubmed.ncbi.nlm.nih.gov/26488693/ DOI: 10.1056/nejmoa1506197
tissue_or_cell_type
Skin cancer counts
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 1431–1443
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · ONTRAC double-blind randomized trial; 386 high-risk participants with at least two recent nonmelanoma skin cancers · source_derived_draft · unverified_draft
### nia-clin-ontrac-skin During ONTRAC treatment, new nonmelanoma skin cancers were 23% lower with nicotinamide than placebo (95% CI 4–38%); there was no evidence of benefit after discontinuation. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Nicotinamide reduced new skin cancers during treatment in this selected high-risk group; protection was not shown to persist after stopping. organism: Homo sapiens tissue_or_cell_type: Skin cancer counts experimental_model: ONTRAC double-blind randomized trial; 386 high-risk participants with at least two recent nonmelanoma skin cancers limitations: Selected high-risk population; this is pharmacological prevention, not proof of deficiency. Combined endpoint differs from subtype effects. Results do not establish efficacy in every population or after treatment stops. exposure: Nicotinamide 500 mg twice daily for 12 months; observation for a further six months cross_nutrient: Niacin precursor form and the measured endpoint are separate graph entities. evidence_span: {"source_cache": "artifacts/niacin-clinical-sources/chen2015.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "7a305aa1d363f375f8cb640b5ddc5f77517f0229a6041558e392d7a07e198aa8", "start_char": 0, "end_char": 2368, "text_sha256": "7a305aa1d363f375f8cb640b5ddc5f77517f0229a6041558e392d7a07e198aa8"} [nia-clin-chen2015] A Phase 3 Randomized Trial of Nicotinamide for Skin-Cancer Chemoprevention. (2015). https://pubmed.ncbi.nlm.nih.gov/26488693/ DOI: 10.1056/nejmoa1506197
Complete structured claim and evidence
ONTRANS recorded 207 versus 210 new keratinocyte cancers with nicotinamide and placebo: rate ratio 1.0, 95% CI 0.8–1.3.
Nicotinamide → New keratinocyte skin cancer incidence source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Niacin precursor form and the measured endpoint are separate graph entities.
evidence_span
{"source_cache": "artifacts/niacin-clinical-sources/allen2023.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "0331a413552524d52730cd68ea35a70b589a37aa0a29d25bbc7b6f4777dbdcbd", "start_char": 0, "end_char": 2229, "text_sha256": "0331a413552524d52730cd68ea35a70b589a37aa0a29d25bbc7b6f4777dbdcbd"}
experimental_model
ONTRANS double-blind randomized trial; 158 solid-organ transplant recipients with recurrent keratinocyte cancers
exposure
Nicotinamide 500 mg twice daily versus placebo for 12 months
limitations
Trial stopped early because of poor recruitment. Population differs materially from immunocompetent ONTRAC participants; neither the population difference nor different statistical results alone constitutes a research contradiction.
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 daily amount did not show a skin-cancer reduction in this smaller transplant-recipient trial.
primary_references
[nia-clin-allen2023] Nicotinamide for Skin-Cancer Chemoprevention in Transplant Recipients. (2023). https://pubmed.ncbi.nlm.nih.gov/36856616/ DOI: 10.1056/nejmoa2203086
tissue_or_cell_type
Skin cancer counts
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 1445–1457
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · ONTRANS double-blind randomized trial; 158 solid-organ transplant recipients with recurrent keratinocyte cancers · source_derived_draft · unverified_draft
### nia-clin-ontrans-skin ONTRANS recorded 207 versus 210 new keratinocyte cancers with nicotinamide and placebo: rate ratio 1.0, 95% CI 0.8–1.3. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The same daily amount did not show a skin-cancer reduction in this smaller transplant-recipient trial. organism: Homo sapiens tissue_or_cell_type: Skin cancer counts experimental_model: ONTRANS double-blind randomized trial; 158 solid-organ transplant recipients with recurrent keratinocyte cancers limitations: Trial stopped early because of poor recruitment. Population differs materially from immunocompetent ONTRAC participants; neither the population difference nor different statistical results alone constitutes a research contradiction. exposure: Nicotinamide 500 mg twice daily versus placebo for 12 months cross_nutrient: Niacin precursor form and the measured endpoint are separate graph entities. evidence_span: {"source_cache": "artifacts/niacin-clinical-sources/allen2023.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "0331a413552524d52730cd68ea35a70b589a37aa0a29d25bbc7b6f4777dbdcbd", "start_char": 0, "end_char": 2229, "text_sha256": "0331a413552524d52730cd68ea35a70b589a37aa0a29d25bbc7b6f4777dbdcbd"} [nia-clin-allen2023] Nicotinamide for Skin-Cancer Chemoprevention in Transplant Recipients. (2023). https://pubmed.ncbi.nlm.nih.gov/36856616/ DOI: 10.1056/nejmoa2203086
Complete structured claim and evidence
Six weeks of NR increased PBMC NAD+ by approximately 60% relative to placebo; the NADP+ increase was not statistically significant.
Nicotinamide riboside → PBMC NAD+ content source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Nicotinamide adenine dinucleotide, oxidized (measured_pool); Oxidized nicotinamide adenine dinucleotide phosphate (separate_measured_pool)
evidence_span
{"source_cache": "artifacts/niacin-clinical-sources/martens2018.txt", "locator": "Primary full report; exact character range, zero-based and end-exclusive", "file_sha256": "6743a5d9ad919ee67fb74af7f173b24bda66943d9c8878d6bc3bb72c80b2c37e", "start_char": 14418, "end_char": 14971, "text_sha256": "412dc909ef2a01bb3f0b5c429c6b594e084262779bbf4e6ad4005f0f1edb8767"}
experimental_model
Randomized double-blind crossover; 30 randomized, 24 healthy adults aged 55–79 completed
exposure
Nicotinamide riboside chloride 500 mg twice daily versus placebo, six weeks each
limitations
Small short trial, no formal washout, directional tests; secondary endpoints adjusted for multiple comparisons. PBMC NAD is not all-tissue NAD or evidence of lifespan extension.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Homo sapiens
plain_language
NR raised NAD in sampled blood immune cells, while a matching rise in NADP was not established.
primary_references
[nia-clin-martens2018] Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. (2018). https://pubmed.ncbi.nlm.nih.gov/29599478/ DOI: 10.1038/s41467-018-03421-7
tissue_or_cell_type
Peripheral blood mononuclear cells and vascular physiology
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 1459–1471
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized double-blind crossover; 30 randomized, 24 healthy adults aged 55–79 completed · source_derived_draft · unverified_draft
### nia-clin-nr-pbmc Six weeks of NR increased PBMC NAD+ by approximately 60% relative to placebo; the NADP+ increase was not statistically significant. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: NR raised NAD in sampled blood immune cells, while a matching rise in NADP was not established. organism: Homo sapiens tissue_or_cell_type: Peripheral blood mononuclear cells and vascular physiology experimental_model: Randomized double-blind crossover; 30 randomized, 24 healthy adults aged 55–79 completed limitations: Small short trial, no formal washout, directional tests; secondary endpoints adjusted for multiple comparisons. PBMC NAD is not all-tissue NAD or evidence of lifespan extension. exposure: Nicotinamide riboside chloride 500 mg twice daily versus placebo, six weeks each cross_nutrient: Nicotinamide adenine dinucleotide, oxidized (measured_pool); Oxidized nicotinamide adenine dinucleotide phosphate (separate_measured_pool) evidence_span: {"source_cache": "artifacts/niacin-clinical-sources/martens2018.txt", "locator": "Primary full report; exact character range, zero-based and end-exclusive", "file_sha256": "6743a5d9ad919ee67fb74af7f173b24bda66943d9c8878d6bc3bb72c80b2c37e", "start_char": 14418, "end_char": 14971, "text_sha256": "412dc909ef2a01bb3f0b5c429c6b594e084262779bbf4e6ad4005f0f1edb8767"} [nia-clin-martens2018] Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. (2018). https://pubmed.ncbi.nlm.nih.gov/29599478/ DOI: 10.1038/s41467-018-03421-7
Complete structured claim and evidence
The observed decrease in aortic pulse-wave velocity did not reach statistical significance after multiple-comparison correction; carotid compliance and brachial flow-mediated dilation showed no effect.
Nicotinamide riboside → Aortic pulse-wave velocity source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Niacin precursor form and the measured endpoint are separate graph entities.
evidence_span
{"source_cache": "artifacts/niacin-clinical-sources/martens2018.txt", "locator": "Primary full report; exact character range, zero-based and end-exclusive", "file_sha256": "6743a5d9ad919ee67fb74af7f173b24bda66943d9c8878d6bc3bb72c80b2c37e", "start_char": 21021, "end_char": 21948, "text_sha256": "f7cee4adec07fb2c817d28092fb58a099173a569a7f20c6421687b8d995d31d2"}
experimental_model
Randomized double-blind crossover; 30 randomized, 24 healthy adults aged 55–79 completed
exposure
Nicotinamide riboside chloride 500 mg twice daily versus placebo, six weeks each
limitations
Small short trial, no formal washout, directional tests; secondary endpoints adjusted for multiple comparisons. PBMC NAD is not all-tissue NAD or evidence of lifespan extension.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Homo sapiens
plain_language
A higher blood NAD level was clearer than the exploratory vascular benefit in this trial.
primary_references
[nia-clin-martens2018] Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. (2018). https://pubmed.ncbi.nlm.nih.gov/29599478/ DOI: 10.1038/s41467-018-03421-7
tissue_or_cell_type
Peripheral blood mononuclear cells and vascular physiology
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 1473–1485
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized double-blind crossover; 30 randomized, 24 healthy adults aged 55–79 completed · source_derived_draft · unverified_draft
### nia-clin-nr-vascular-bound The observed decrease in aortic pulse-wave velocity did not reach statistical significance after multiple-comparison correction; carotid compliance and brachial flow-mediated dilation showed no effect. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A higher blood NAD level was clearer than the exploratory vascular benefit in this trial. organism: Homo sapiens tissue_or_cell_type: Peripheral blood mononuclear cells and vascular physiology experimental_model: Randomized double-blind crossover; 30 randomized, 24 healthy adults aged 55–79 completed limitations: Small short trial, no formal washout, directional tests; secondary endpoints adjusted for multiple comparisons. PBMC NAD is not all-tissue NAD or evidence of lifespan extension. exposure: Nicotinamide riboside chloride 500 mg twice daily versus placebo, six weeks each cross_nutrient: Niacin precursor form and the measured endpoint are separate graph entities. evidence_span: {"source_cache": "artifacts/niacin-clinical-sources/martens2018.txt", "locator": "Primary full report; exact character range, zero-based and end-exclusive", "file_sha256": "6743a5d9ad919ee67fb74af7f173b24bda66943d9c8878d6bc3bb72c80b2c37e", "start_char": 21021, "end_char": 21948, "text_sha256": "f7cee4adec07fb2c817d28092fb58a099173a569a7f20c6421687b8d995d31d2"} [nia-clin-martens2018] Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. (2018). https://pubmed.ncbi.nlm.nih.gov/29599478/ DOI: 10.1038/s41467-018-03421-7
Complete structured claim and evidence
Insulin-stimulated glucose disposal per kg fat-free mass increased by 25±7% after ten weeks of NMN, while the placebo group showed no corresponding change.
NMN → Insulin-stimulated glucose uptake source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Insulin (test_signal)
evidence_span
{"source_cache": "artifacts/niacin-clinical-sources/yoshino2021.txt", "locator": "Primary full report; exact character range, zero-based and end-exclusive", "file_sha256": "e4999dc5b9d3392d8180280727c424044b35249bb24c999c3bc863cd23e6c856", "start_char": 6120, "end_char": 7140, "text_sha256": "152262160f005f7aac5e078287acca1db556d35a8645d8892492723992dec2dc"}
experimental_model
Randomized double-blind trial; 25 overweight or obese postmenopausal women with prediabetes completed
exposure
NMN 250 mg/day for 10 weeks; 13 NMN and 12 placebo participants
limitations
Small selected female cohort. Tissue NAD concentration, NAD turnover and clinical outcomes differ. No lifespan or diabetes-prevention endpoint. Positive muscle findings do not establish whole-body or cross-population benefit.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Homo sapiens
plain_language
In this small group of women, muscle responded better to insulin during the clamp test.
primary_references
[nia-clin-yoshino2021] Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. (2021). https://pubmed.ncbi.nlm.nih.gov/33888596/ DOI: 10.1126/science.abe9985
tissue_or_cell_type
Skeletal muscle, PBMCs, liver and adipose insulin sensitivity
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 1487–1499
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized double-blind trial; 25 overweight or obese postmenopausal women with prediabetes completed · source_derived_draft · unverified_draft
### nia-clin-nmn-muscle-insulin Insulin-stimulated glucose disposal per kg fat-free mass increased by 25±7% after ten weeks of NMN, while the placebo group showed no corresponding change. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: In this small group of women, muscle responded better to insulin during the clamp test. organism: Homo sapiens tissue_or_cell_type: Skeletal muscle, PBMCs, liver and adipose insulin sensitivity experimental_model: Randomized double-blind trial; 25 overweight or obese postmenopausal women with prediabetes completed limitations: Small selected female cohort. Tissue NAD concentration, NAD turnover and clinical outcomes differ. No lifespan or diabetes-prevention endpoint. Positive muscle findings do not establish whole-body or cross-population benefit. exposure: NMN 250 mg/day for 10 weeks; 13 NMN and 12 placebo participants cross_nutrient: Insulin (test_signal) evidence_span: {"source_cache": "artifacts/niacin-clinical-sources/yoshino2021.txt", "locator": "Primary full report; exact character range, zero-based and end-exclusive", "file_sha256": "e4999dc5b9d3392d8180280727c424044b35249bb24c999c3bc863cd23e6c856", "start_char": 6120, "end_char": 7140, "text_sha256": "152262160f005f7aac5e078287acca1db556d35a8645d8892492723992dec2dc"} [nia-clin-yoshino2021] 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
Muscle insulin-stimulated AKT and mTOR phosphorylation and total abundance increased after NMN but not placebo.
NMN → Muscle insulin-stimulated AKT and mTOR signaling source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Insulin (stimulus)
evidence_span
{"source_cache": "artifacts/niacin-clinical-sources/yoshino2021.txt", "locator": "Primary full report; exact character range, zero-based and end-exclusive", "file_sha256": "e4999dc5b9d3392d8180280727c424044b35249bb24c999c3bc863cd23e6c856", "start_char": 7141, "end_char": 7815, "text_sha256": "31871685ed5bb9ceb845b035d50807218311c0fad543f690e5ab924ba9872d0d"}
experimental_model
Randomized double-blind trial; 25 overweight or obese postmenopausal women with prediabetes completed
exposure
NMN 250 mg/day for 10 weeks; 13 NMN and 12 placebo participants
limitations
Small selected female cohort. Tissue NAD concentration, NAD turnover and clinical outcomes differ. No lifespan or diabetes-prevention endpoint. Positive muscle findings do not establish whole-body or cross-population benefit.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Homo sapiens
plain_language
The muscle response was accompanied by changes in insulin-signaling proteins.
primary_references
[nia-clin-yoshino2021] Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. (2021). https://pubmed.ncbi.nlm.nih.gov/33888596/ DOI: 10.1126/science.abe9985
tissue_or_cell_type
Skeletal muscle, PBMCs, liver and adipose insulin sensitivity
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 1501–1513
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized double-blind trial; 25 overweight or obese postmenopausal women with prediabetes completed · source_derived_draft · unverified_draft
### nia-clin-nmn-muscle-signal Muscle insulin-stimulated AKT and mTOR phosphorylation and total abundance increased after NMN but not placebo. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The muscle response was accompanied by changes in insulin-signaling proteins. organism: Homo sapiens tissue_or_cell_type: Skeletal muscle, PBMCs, liver and adipose insulin sensitivity experimental_model: Randomized double-blind trial; 25 overweight or obese postmenopausal women with prediabetes completed limitations: Small selected female cohort. Tissue NAD concentration, NAD turnover and clinical outcomes differ. No lifespan or diabetes-prevention endpoint. Positive muscle findings do not establish whole-body or cross-population benefit. exposure: NMN 250 mg/day for 10 weeks; 13 NMN and 12 placebo participants cross_nutrient: Insulin (stimulus) evidence_span: {"source_cache": "artifacts/niacin-clinical-sources/yoshino2021.txt", "locator": "Primary full report; exact character range, zero-based and end-exclusive", "file_sha256": "e4999dc5b9d3392d8180280727c424044b35249bb24c999c3bc863cd23e6c856", "start_char": 7141, "end_char": 7815, "text_sha256": "31871685ed5bb9ceb845b035d50807218311c0fad543f690e5ab924ba9872d0d"} [nia-clin-yoshino2021] 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
Muscle NAD+ content did not rise after NMN even though PBMC NAD+ and muscle methylated niacin metabolites increased; authors interpreted the latter as consistent with increased turnover.
NMN → Skeletal muscle NAD+ content source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Nicotinamide adenine dinucleotide, oxidized (coenzyme); PBMC NAD+ content (separate_compartment_marker); N1-methylnicotinamide (muscle_metabolite)
evidence_span
{"source_cache": "artifacts/niacin-clinical-sources/yoshino2021.txt", "locator": "Primary full report; exact character range, zero-based and end-exclusive", "file_sha256": "e4999dc5b9d3392d8180280727c424044b35249bb24c999c3bc863cd23e6c856", "start_char": 4842, "end_char": 6119, "text_sha256": "bb73c5ac9d2ac503143ede8627aaa6be34763fdd501bf48a32528a332b89016c"}
experimental_model
Randomized double-blind trial; 25 overweight or obese postmenopausal women with prediabetes completed
exposure
NMN 250 mg/day for 10 weeks; 13 NMN and 12 placebo participants
limitations
Small selected female cohort. Tissue NAD concentration, NAD turnover and clinical outcomes differ. No lifespan or diabetes-prevention endpoint. Positive muscle findings do not establish whole-body or cross-population benefit.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Homo sapiens
plain_language
More NAD-related activity did not necessarily mean a larger standing NAD pool in muscle.
primary_references
[nia-clin-yoshino2021] Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. (2021). https://pubmed.ncbi.nlm.nih.gov/33888596/ DOI: 10.1126/science.abe9985
tissue_or_cell_type
Skeletal muscle, PBMCs, liver and adipose insulin sensitivity
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 1515–1527
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized double-blind trial; 25 overweight or obese postmenopausal women with prediabetes completed · source_derived_draft · unverified_draft
### nia-clin-nmn-muscle-nad Muscle NAD+ content did not rise after NMN even though PBMC NAD+ and muscle methylated niacin metabolites increased; authors interpreted the latter as consistent with increased turnover. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: More NAD-related activity did not necessarily mean a larger standing NAD pool in muscle. organism: Homo sapiens tissue_or_cell_type: Skeletal muscle, PBMCs, liver and adipose insulin sensitivity experimental_model: Randomized double-blind trial; 25 overweight or obese postmenopausal women with prediabetes completed limitations: Small selected female cohort. Tissue NAD concentration, NAD turnover and clinical outcomes differ. No lifespan or diabetes-prevention endpoint. Positive muscle findings do not establish whole-body or cross-population benefit. exposure: NMN 250 mg/day for 10 weeks; 13 NMN and 12 placebo participants cross_nutrient: Nicotinamide adenine dinucleotide, oxidized (coenzyme); PBMC NAD+ content (separate_compartment_marker); N1-methylnicotinamide (muscle_metabolite) evidence_span: {"source_cache": "artifacts/niacin-clinical-sources/yoshino2021.txt", "locator": "Primary full report; exact character range, zero-based and end-exclusive", "file_sha256": "e4999dc5b9d3392d8180280727c424044b35249bb24c999c3bc863cd23e6c856", "start_char": 4842, "end_char": 6119, "text_sha256": "bb73c5ac9d2ac503143ede8627aaa6be34763fdd501bf48a32528a332b89016c"} [nia-clin-yoshino2021] 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 NMN trial did not find improved hepatic or adipose tissue insulin sensitivity; fasting metabolic measures, body composition and liver fat were also unchanged.
NMN → Hepatic insulin sensitivity source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Adipose tissue insulin sensitivity (parallel_null_endpoint)
evidence_span
{"source_cache": "artifacts/niacin-clinical-sources/yoshino2021.txt", "locator": "Primary full report; exact character range, zero-based and end-exclusive", "file_sha256": "e4999dc5b9d3392d8180280727c424044b35249bb24c999c3bc863cd23e6c856", "start_char": 6120, "end_char": 7140, "text_sha256": "152262160f005f7aac5e078287acca1db556d35a8645d8892492723992dec2dc"}
experimental_model
Randomized double-blind trial; 25 overweight or obese postmenopausal women with prediabetes completed
exposure
NMN 250 mg/day for 10 weeks; 13 NMN and 12 placebo participants
limitations
Small selected female cohort. Tissue NAD concentration, NAD turnover and clinical outcomes differ. No lifespan or diabetes-prevention endpoint. Positive muscle findings do not establish whole-body or cross-population benefit.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Homo sapiens
plain_language
The muscle result did not extend to all insulin-responsive organs or to a general metabolic improvement.
primary_references
[nia-clin-yoshino2021] Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. (2021). https://pubmed.ncbi.nlm.nih.gov/33888596/ DOI: 10.1126/science.abe9985
tissue_or_cell_type
Skeletal muscle, PBMCs, liver and adipose insulin sensitivity
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 1529–1541
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized double-blind trial; 25 overweight or obese postmenopausal women with prediabetes completed · source_derived_draft · unverified_draft
### nia-clin-nmn-liver-insulin The NMN trial did not find improved hepatic or adipose tissue insulin sensitivity; fasting metabolic measures, body composition and liver fat were also unchanged. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The muscle result did not extend to all insulin-responsive organs or to a general metabolic improvement. organism: Homo sapiens tissue_or_cell_type: Skeletal muscle, PBMCs, liver and adipose insulin sensitivity experimental_model: Randomized double-blind trial; 25 overweight or obese postmenopausal women with prediabetes completed limitations: Small selected female cohort. Tissue NAD concentration, NAD turnover and clinical outcomes differ. No lifespan or diabetes-prevention endpoint. Positive muscle findings do not establish whole-body or cross-population benefit. exposure: NMN 250 mg/day for 10 weeks; 13 NMN and 12 placebo participants cross_nutrient: Adipose tissue insulin sensitivity (parallel_null_endpoint) evidence_span: {"source_cache": "artifacts/niacin-clinical-sources/yoshino2021.txt", "locator": "Primary full report; exact character range, zero-based and end-exclusive", "file_sha256": "e4999dc5b9d3392d8180280727c424044b35249bb24c999c3bc863cd23e6c856", "start_char": 6120, "end_char": 7140, "text_sha256": "152262160f005f7aac5e078287acca1db556d35a8645d8892492723992dec2dc"} [nia-clin-yoshino2021] 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
Twelve weeks of NR did not improve clamp insulin sensitivity, glucose production or disposal, lipid mobilization, resting energy expenditure or body composition in this trial.
Nicotinamide riboside → Insulin-stimulated glucose uptake source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Niacin precursor form and the measured endpoint are separate graph entities.
evidence_span
{"source_cache": "artifacts/niacin-clinical-sources/dollerup2018.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "dd5668627aa4f11bce6460dd6d163248c711dd43b85b6265a4055cf96012b241", "start_char": 0, "end_char": 1987, "text_sha256": "dd5668627aa4f11bce6460dd6d163248c711dd43b85b6265a4055cf96012b241"}
experimental_model
Randomized double-blind trial; 40 sedentary obese insulin-resistant men aged 40–70
exposure
NR 1,000 mg twice daily versus placebo for 12 weeks
limitations
Different precursor and population from the NMN female trial. No efficacy demonstrated for the tested endpoints; short tolerability observations do not establish universal long-term safety.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Homo sapiens
plain_language
NR did not produce a general metabolic improvement in these insulin-resistant men.
primary_references
[nia-clin-dollerup2018] A randomized placebo-controlled clinical trial of nicotinamide riboside in obese men: safety, insulin-sensitivity, and lipid-mobilizing effects. (2018). https://pubmed.ncbi.nlm.nih.gov/29992272/ DOI: 10.1093/ajcn/nqy132
tissue_or_cell_type
Clamp glucose metabolism and body composition
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 1543–1555
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized double-blind trial; 40 sedentary obese insulin-resistant men aged 40–70 · source_derived_draft · unverified_draft
### nia-clin-nr-obese-men Twelve weeks of NR did not improve clamp insulin sensitivity, glucose production or disposal, lipid mobilization, resting energy expenditure or body composition in this trial. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: NR did not produce a general metabolic improvement in these insulin-resistant men. organism: Homo sapiens tissue_or_cell_type: Clamp glucose metabolism and body composition experimental_model: Randomized double-blind trial; 40 sedentary obese insulin-resistant men aged 40–70 limitations: Different precursor and population from the NMN female trial. No efficacy demonstrated for the tested endpoints; short tolerability observations do not establish universal long-term safety. exposure: NR 1,000 mg twice daily versus placebo for 12 weeks cross_nutrient: Niacin precursor form and the measured endpoint are separate graph entities. evidence_span: {"source_cache": "artifacts/niacin-clinical-sources/dollerup2018.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "dd5668627aa4f11bce6460dd6d163248c711dd43b85b6265a4055cf96012b241", "start_char": 0, "end_char": 1987, "text_sha256": "dd5668627aa4f11bce6460dd6d163248c711dd43b85b6265a4055cf96012b241"} [nia-clin-dollerup2018] A randomized placebo-controlled clinical trial of nicotinamide riboside in obese men: safety, insulin-sensitivity, and lipid-mobilizing effects. (2018). https://pubmed.ncbi.nlm.nih.gov/29992272/ DOI: 10.1093/ajcn/nqy132
Complete structured claim and evidence
Higher serum 2PY was associated with three-year major adverse cardiovascular events in both validation cohorts.
N1-methyl-2-pyridone-5-carboxamide (2PY) → Major cardiovascular event incidence source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
cross_nutrient
Niacin precursor form and the measured endpoint are separate graph entities.
evidence_span
{"source_cache": "artifacts/niacin-clinical-sources/ferrell2024.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "09530c87779c7a8db8507c847dcb29ae3b7e439967c9271dec5f7cbda6c33d19", "start_char": 0, "end_char": 2066, "text_sha256": "09530c87779c7a8db8507c847dcb29ae3b7e439967c9271dec5f7cbda6c33d19"}
experimental_model
Prospective stable cardiac patient cohorts with three-year event follow-up
exposure
Discovery cohort 1,162; US validation 2,331 and European validation 832; three-year cardiovascular follow-up; physiological-level mouse metabolite exposure
limitations
Human metabolite associations are not randomized effects of niacin intake. Renal handling and other determinants of levels matter. Mouse exposure results do not prove dietary niacin or supplements caused human events.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Homo sapiens
plain_language
A breakdown-product measurement tracked risk; that does not identify dietary niacin as the cause.
primary_references
[nia-clin-ferrell2024] A terminal metabolite of niacin promotes vascular inflammation and contributes to cardiovascular disease risk. (2024). https://pubmed.ncbi.nlm.nih.gov/38374343/ DOI: 10.1038/s41591-023-02793-8
tissue_or_cell_type
Serum metabolites and clinical cardiovascular outcomes
trigger_kind
biomarker_context Imported condition classification; unverified.
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 1557–1569
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Prospective stable cardiac patient cohorts with three-year event follow-up · source_derived_draft · unverified_draft
### nia-clin-2py-risk Higher serum 2PY was associated with three-year major adverse cardiovascular events in both validation cohorts. Condition category: biomarker_context nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A breakdown-product measurement tracked risk; that does not identify dietary niacin as the cause. organism: Homo sapiens tissue_or_cell_type: Serum metabolites and clinical cardiovascular outcomes experimental_model: Prospective stable cardiac patient cohorts with three-year event follow-up limitations: Human metabolite associations are not randomized effects of niacin intake. Renal handling and other determinants of levels matter. Mouse exposure results do not prove dietary niacin or supplements caused human events. exposure: Discovery cohort 1,162; US validation 2,331 and European validation 832; three-year cardiovascular follow-up; physiological-level mouse metabolite exposure cross_nutrient: Niacin precursor form and the measured endpoint are separate graph entities. evidence_span: {"source_cache": "artifacts/niacin-clinical-sources/ferrell2024.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "09530c87779c7a8db8507c847dcb29ae3b7e439967c9271dec5f7cbda6c33d19", "start_char": 0, "end_char": 2066, "text_sha256": "09530c87779c7a8db8507c847dcb29ae3b7e439967c9271dec5f7cbda6c33d19"} [nia-clin-ferrell2024] A terminal metabolite of niacin promotes vascular inflammation and contributes to cardiovascular disease risk. (2024). https://pubmed.ncbi.nlm.nih.gov/38374343/ DOI: 10.1038/s41591-023-02793-8
Complete structured claim and evidence
Higher serum 4PY was associated with three-year major adverse cardiovascular events in both validation cohorts.
N1-methyl-4-pyridone-3-carboxamide (4PY) → Major cardiovascular event incidence source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
cross_nutrient
Niacin precursor form and the measured endpoint are separate graph entities.
evidence_span
{"source_cache": "artifacts/niacin-clinical-sources/ferrell2024.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "09530c87779c7a8db8507c847dcb29ae3b7e439967c9271dec5f7cbda6c33d19", "start_char": 0, "end_char": 2066, "text_sha256": "09530c87779c7a8db8507c847dcb29ae3b7e439967c9271dec5f7cbda6c33d19"}
experimental_model
Prospective stable cardiac patient cohorts with three-year event follow-up
exposure
Discovery cohort 1,162; US validation 2,331 and European validation 832; three-year cardiovascular follow-up; physiological-level mouse metabolite exposure
limitations
Human metabolite associations are not randomized effects of niacin intake. Renal handling and other determinants of levels matter. Mouse exposure results do not prove dietary niacin or supplements caused human events.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Homo sapiens
plain_language
A second terminal metabolite also tracked risk in the studied cardiac patients.
primary_references
[nia-clin-ferrell2024] A terminal metabolite of niacin promotes vascular inflammation and contributes to cardiovascular disease risk. (2024). https://pubmed.ncbi.nlm.nih.gov/38374343/ DOI: 10.1038/s41591-023-02793-8
tissue_or_cell_type
Serum metabolites and clinical cardiovascular outcomes
trigger_kind
biomarker_context Imported condition classification; unverified.
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 1571–1583
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Prospective stable cardiac patient cohorts with three-year event follow-up · source_derived_draft · unverified_draft
### nia-clin-4py-risk Higher serum 4PY was associated with three-year major adverse cardiovascular events in both validation cohorts. Condition category: biomarker_context nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A second terminal metabolite also tracked risk in the studied cardiac patients. organism: Homo sapiens tissue_or_cell_type: Serum metabolites and clinical cardiovascular outcomes experimental_model: Prospective stable cardiac patient cohorts with three-year event follow-up limitations: Human metabolite associations are not randomized effects of niacin intake. Renal handling and other determinants of levels matter. Mouse exposure results do not prove dietary niacin or supplements caused human events. exposure: Discovery cohort 1,162; US validation 2,331 and European validation 832; three-year cardiovascular follow-up; physiological-level mouse metabolite exposure cross_nutrient: Niacin precursor form and the measured endpoint are separate graph entities. evidence_span: {"source_cache": "artifacts/niacin-clinical-sources/ferrell2024.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "09530c87779c7a8db8507c847dcb29ae3b7e439967c9271dec5f7cbda6c33d19", "start_char": 0, "end_char": 2066, "text_sha256": "09530c87779c7a8db8507c847dcb29ae3b7e439967c9271dec5f7cbda6c33d19"} [nia-clin-ferrell2024] A terminal metabolite of niacin promotes vascular inflammation and contributes to cardiovascular disease risk. (2024). https://pubmed.ncbi.nlm.nih.gov/38374343/ DOI: 10.1038/s41591-023-02793-8
Complete structured claim and evidence
Physiological-level 4PY exposure, unlike structural isomer 2PY, induced vascular VCAM-1 expression and leukocyte adherence in mice.
N1-methyl-4-pyridone-3-carboxamide (4PY) → Mouse endothelial Vcam1 expression source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Mouse vascular cell adhesion molecule 1 / Vcam1 (induced_protein); Leukocyte adherence to vascular endothelium (measured_consequence); N1-methyl-2-pyridone-5-carboxamide (2PY) (negative_comparator)
evidence_span
{"source_cache": "artifacts/niacin-clinical-sources/ferrell2024.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "09530c87779c7a8db8507c847dcb29ae3b7e439967c9271dec5f7cbda6c33d19", "start_char": 0, "end_char": 2066, "text_sha256": "09530c87779c7a8db8507c847dcb29ae3b7e439967c9271dec5f7cbda6c33d19"}
experimental_model
Prospective cardiac cohorts, genetic associations, and separate mouse metabolite exposures
exposure
Discovery cohort 1,162; US validation 2,331 and European validation 832; three-year cardiovascular follow-up; physiological-level mouse metabolite exposure
limitations
Human metabolite associations are not randomized effects of niacin intake. Renal handling and other determinants of levels matter. Mouse exposure results do not prove dietary niacin or supplements caused human events.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Mus musculus
plain_language
In mice, one breakdown product directly promoted a vessel-wall adhesion response; its close chemical relative did not.
primary_references
[nia-clin-ferrell2024] A terminal metabolite of niacin promotes vascular inflammation and contributes to cardiovascular disease risk. (2024). https://pubmed.ncbi.nlm.nih.gov/38374343/ DOI: 10.1038/s41591-023-02793-8
tissue_or_cell_type
Circulating metabolites and mouse vascular endothelium
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 1585–1597
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Prospective cardiac cohorts, genetic associations, and separate mouse metabolite exposures · source_derived_draft · unverified_draft
### nia-clin-4py-mouse-vcam Physiological-level 4PY exposure, unlike structural isomer 2PY, induced vascular VCAM-1 expression and leukocyte adherence in mice. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: In mice, one breakdown product directly promoted a vessel-wall adhesion response; its close chemical relative did not. organism: Mus musculus tissue_or_cell_type: Circulating metabolites and mouse vascular endothelium experimental_model: Prospective cardiac cohorts, genetic associations, and separate mouse metabolite exposures limitations: Human metabolite associations are not randomized effects of niacin intake. Renal handling and other determinants of levels matter. Mouse exposure results do not prove dietary niacin or supplements caused human events. exposure: Discovery cohort 1,162; US validation 2,331 and European validation 832; three-year cardiovascular follow-up; physiological-level mouse metabolite exposure cross_nutrient: Mouse vascular cell adhesion molecule 1 / Vcam1 (induced_protein); Leukocyte adherence to vascular endothelium (measured_consequence); N1-methyl-2-pyridone-5-carboxamide (2PY) (negative_comparator) evidence_span: {"source_cache": "artifacts/niacin-clinical-sources/ferrell2024.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "09530c87779c7a8db8507c847dcb29ae3b7e439967c9271dec5f7cbda6c33d19", "start_char": 0, "end_char": 2066, "text_sha256": "09530c87779c7a8db8507c847dcb29ae3b7e439967c9271dec5f7cbda6c33d19"} [nia-clin-ferrell2024] A terminal metabolite of niacin promotes vascular inflammation and contributes to cardiovascular disease risk. (2024). https://pubmed.ncbi.nlm.nih.gov/38374343/ DOI: 10.1038/s41591-023-02793-8
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.

Experimental NAPRT loss blocks the nicotinic-acid response

Condition: machinery_impairment · Experimental knockdown of NAPRT expression

Normal role: NAPRT admits nicotinic acid to NAD synthesis.

Recorded consequence: Loss of the nicotinic-acid-driven rise in cellular NAD

Scope: Machinery impairment in the tested cells

Mouse Nmrk1 loss impairs precursor use in hepatocytes

Condition: machinery_impairment · Constitutive homozygous Nmrk1 ablation

Normal role: NRK1 enables NR-dependent NAD synthesis.

Recorded consequence: Loss of NR- and NMN-driven NAD elevation in isolated hepatocytes

Scope: Genetic machinery impairment, not dietary niacin deficiency

HPF1 loss during DNA damage

Condition: machinery_impairment · HPF1 deletion in U2OS cells

Normal role: NAD cleavage supports regulated protein modification or signaling; abnormal machinery changes are distinct from dietary niacin shortage.

Recorded consequence: Near-loss of histone serine ADP-ribosylation

Scope: Human U2OS culture; H2O2 treatment

Loss of SARM1 NADase activity

Condition: machinery_impairment · E642A substitution in SARM1

Normal role: NAD cleavage supports regulated protein modification or signaling; abnormal machinery changes are distinct from dietary niacin shortage.

Recorded consequence: Loss of NAD cleavage in vitro and resistance to injury-associated NAD depletion in neuronal reconstitution

Scope: Human SARM1 constructs; embryonic mouse DRG neurons

NADK2 machinery impairment

Condition: machinery_impairment · Experimental knockdown or pathogenic NADK2 alteration

Normal role: NAD import and NAD kinase activity establish distinct mitochondrial redox pools.

Recorded consequence: Reduced mitochondrial NADP(H) synthesis or dependent enzyme function

Scope: HEK293A knockdown and separately patient-derived fibroblasts.

NNT reversal during pathological workload

Condition: machinery_impairment · Cardiac pressure overload / pathological metabolic demand

Normal role: NAD import and NAD kinase activity establish distinct mitochondrial redox pools.

Recorded consequence: NADPH consumption by reverse transhydrogenase flux

Scope: Mouse cardiac model; not nutrient depletion.

Mitochondrial NAD import impairment

Condition: machinery_impairment · RNA interference or CRISPR SLC25A51 knockout

Normal role: NAD import and NAD kinase activity establish distinct mitochondrial redox pools.

Recorded consequence: Reduced mitochondrial NAD availability despite preserved whole-cell NAD

Scope: Human cultured cells and isolated mitochondria.

Low niacin and tryptophan supply reduces erythrocyte NAD

Condition: nutrient_deficiency · Controlled low niacin-equivalent diets, 6.1 or 10.1 NE/day.

Normal role: Available precursors and functioning enzymes sustain the measured pathway or nutrient-derived pool.

Recorded consequence: Erythrocyte NAD fell while NADP was comparatively preserved; repletion raised NAD.

Scope: The specified study population or experimental model.

Prolonged low niacin plus low tryptophan can produce pellagra

Condition: nutrient_deficiency · Prolonged corn-based experimental diet low in both niacin and tryptophan despite other B-vitamin supplements.

Normal role: Available precursors and functioning enzymes sustain the measured pathway or nutrient-derived pool.

Recorded consequence: Mucosal, gastrointestinal and skin lesions developed with variable timing and improved after precursor repletion.

Scope: The specified study population or experimental model.

Inherited HAAO or KYNU defects interrupt NAD synthesis

Condition: machinery_impairment · Biallelic loss-of-function variants in kynurenine-pathway enzymes.

Normal role: Available precursors and functioning enzymes sustain the measured pathway or nutrient-derived pool.

Recorded consequence: Reduced circulating NAD and congenital malformations were found in the reported families.

Scope: The specified study population or experimental model.

Serotonin-producing tumors can accompany low niacin markers

Condition: biomarker_context · Selected serotonin-producing NET patients with low tryptophan or relevant symptoms.

Normal role: Available precursors and functioning enzymes sustain the measured pathway or nutrient-derived pool.

Recorded consequence: Low urinary N1-methylnicotinamide was common; urinary output increased after prescribed niacin.

Scope: The specified study population or experimental model.

Receptor-signaling machinery changes nicotinic-acid flushing

Condition: machinery_impairment · Knockout of Hcar2 or Arrb1 in the respective mouse studies.

Normal role: Nicotinic acid activates receptor signaling that can produce cutaneous flushing.

Recorded consequence: Loss or reduction of the flushing response; bone-marrow rescue and preserved fatty-acid response identify distinct signaling branches.

Scope: Separate genetically manipulated mouse experiments using pharmacological nicotinic acid.

Higher terminal niacin metabolites accompany cardiovascular risk

Condition: biomarker_context · Higher measured serum 2PY or 4PY in the studied cardiac populations.

Normal role: Available precursors and functioning enzymes sustain the measured pathway or nutrient-derived pool.

Recorded consequence: Associations with three-year events; separate mouse work identified a vascular effect of 4PY.

Scope: The specified study population or experimental model.

The sources

Every document behind this chapter is preserved word for word. Open one to read it in full with its recorded conflicts marked in place.

Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
L-Lysine: mechanism-first literature curation (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Selenium: literature corrections and mechanism additionsMetabolic Ledger literature curation, 17 September 2026; primary papers linked individually · secondary_verifiedRead preserved source
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source

Recorded disagreements

Where two sources say different things, both are kept and the difference is explained. You can discuss a disagreement or propose a mechanism that might account for it.

Open questions in this collection

Questions the curators could not answer from the sources in front of them, kept here with the reason each one is still open. These are gaps in this collection, not findings or proof that no one has studied them.

What sustained precursor regimens improve clinically important outcomes in which people, beyond changing an NAD measurement?Selected trials are short or population-specific; none establishes general anti-aging efficacy.
Which processes connect dietary niacin shortage to each tissue lesion in human pellagra?The clinical depletion study documents variable lesions and recovery but does not independently isolate every molecular pathway.
How do dietary intake, renal handling and intracellular flux jointly determine 2PY and 4PY cardiovascular associations?Biomarker cohorts plus mouse mechanisms do not establish a safe or harmful universal intake threshold.
Why does NNMT alter methyl-donor balance in some cell conditions while short human methionine restriction preserves measured nicotinamide disposal?Different specimens, donor availability and endpoints; the human challenge did not measure all cellular methylation reactions.
Whether NNMT-mediated methyl-donor use during ordinary niacin replacement causes clinically important methyl depletion is not established by these cancer-cell experiments.Engineered expression and culture methionine exposures cannot stand in for whole-body nutritional repletion.
These assays do not determine whether raising NAD through supplementation improves long-term human health.Biochemical cleavage and experimental injury models do not measure clinical benefit.
The 1998 CD38 paper rejects an obligatory cADPR intermediate for the hydrolytic route; an overlapping historical primary comparator has not been curated here.Potential historical mechanistic disagreement requires review of both primary interpretations; no orange conflict is asserted from a single paper.
The relative use of extracellular NMN conversion and possible intact NMN entry across human tissues is not established by the HepG2 and mouse-hepatocyte experiments curated here.No generalized transport or clinical efficacy claim follows from these specific models. No orange conflict is manufactured from cross-model differences.
The collection does not derive a human B2, B6 or iron supplementation requirement from the cofactor-dependent tryptophan pathway.Purified proteins, genetic interruptions and experimental nutrient deficiencies address different causal questions.
The magnitude of dietary magnesium or niacin shortage needed to limit human mitochondrial NADP synthesis is not established by these studies.Purified MgATP assays and genetic impairment cannot define nutritional thresholds.
Physiological contributions of NADK2 polyphosphate utilization and NADH phosphorylation remain unquantified here.In vitro donor specificity and relative activity are not compartment-resolved flux measurements.
NNT forward and reverse flux depend on energetic and redox context.The selected cardiac pressure-overload result cannot establish the direction in every tissue or disease.

Chapters are assembled from supplied drafts and curated literature summaries. Statements remain unverified against the primary studies, and the ledger is not medical advice.

Evidence, AI assistance and curation standards

Niacin (vitamin B3)

The mechanisms

Human KMO membrane assays measured kynurenine conversion to 3-hydroxykynurenine with NADPH; at 200 micromolar NADPH, kynurenine Km was 2 micromolar.

Kmo knockout reduced quinolinate to about 3% of wild-type liver content but about 80% of wild-type brain content.

Measured liver and brain NAD+ contents were not significantly different between Kmo-knockout and wild-type mice.

Riboflavin-deficient baboons excreted approximately one tenth as much urinary 3-hydroxykynurenine in the reported dietary comparison.

Human kynureninase crystallography resolves the PLP-containing active-site architecture.

Human KYNU cleaves 3-hydroxykynurenine to 3-hydroxyanthranilate and alanine using PLP.

Under niacin-free feeding, B6-free rats had lower apparent tryptophan-to-niacin conversion than rats receiving B6.

Human SIRT1 removes acetylation from histone H4 Lys16 in an NAD+-dependent reaction.

SELENOO can split NAD into two smaller molecules.

Human DLD uses bound FAD and transiently bound NAD+ to oxidize dihydrolipoamide; NADH-bound structures place its nicotinamide ring beside FAD.

GSR reduces one glutathione-disulfide molecule to two reduced glutathione molecules using the NADPH/FAD catalytic relay.

Purified full-length human MTHFR had apparent Km values of 35.5 micromolar for NADPH and 3760 micromolar for NADH.

Reconstituted assays showed human MTRR sufficient to support NADPH-dependent activity of cobalamin-dependent methionine synthase.

Recombinant human RDH10 oxidized all-trans-retinol with NAD+ in microsomal assays.

RDH10-activated DHRS3 reduced all-trans-retinal to retinol preferentially using NADPH.

Dialyzed liver cytosol from selenium-deficient rats lost NADPH-dependent ascorbyl-radical reducing activity attributed to thioredoxin reductase.

Rat liver microsomes reduced ascorbyl radical using NADH, and this activity was insensitive to selenium depletion.

The active human CYP27B1 reconstitution supplied human adrenodoxin reductase and NADPH upstream of human adrenodoxin.

Human NAPRT catalyzes phosphoribosyl transfer from PRPP to nicotinic acid, producing nicotinic acid mononucleotide and pyrophosphate.

Inorganic phosphate activated purified recombinant human NAPRT in the reported kinetic experiments.

ATP stimulated or inhibited recombinant human NAPRT depending on low or high substrate saturation in the reported kinetic assays.

NAPRT knockdown reversed the rise in cellular NAD caused by nicotinic acid in the cultured human cells studied.

Purified recombinant human NMNAT2 has adenylyltransferase activity toward NMN, supporting NAD+ formation.

Purified recombinant human NMNAT2 has adenylyltransferase activity toward nicotinic acid mononucleotide, supporting NaAD formation.

Purified human NADSYN1 catalyzed ATP-dependent NAD+ production from nicotinic acid adenine dinucleotide in glutamine-supported assays.

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.

Purified human NADSYN1 also supported NAD+ formation with free ammonia; its reported catalytic efficiencies for glutamine and ammonia were similar, 0.45 and 0.49 per second per millimolar.

Human NAMPT converts nicotinamide and PRPP to nicotinamide mononucleotide and pyrophosphate.

NMR monitoring demonstrated reversibility of the purified human NAMPT reaction; the measured equilibrium constant was 0.14 under the study conditions.

Transient overexpression of active mouse NRK1 made NIH/3T3 fibroblasts responsive to nicotinamide riboside with increased cellular NAD+; the tested catalytically inactive kinase failed to support the response.

Transient overexpression of active mouse NRK2 made NIH/3T3 fibroblasts responsive to nicotinamide riboside with increased cellular NAD+; the tested catalytically inactive kinase failed to support the response.

Primary hepatocytes from Nmrk1-knockout mice failed to increase NAD+ after NR treatment, whereas wild-type hepatocytes responded.

Primary hepatocytes from Nmrk1-knockout mice failed to increase NAD+ after NMN treatment, whereas wild-type hepatocytes responded.

In serum- and nicotinamide-free HepG2 cultures, oxygen-18-labelled NR entered intracellular NR, NMN and NAD+ pools without detectable labelled NMN or nicotinamide appearing in the medium over 24 hours.

Oxygen-18-labelled NMN supplied to HepG2 cultures generated extracellular labelled NR; at seven hours approximately 80% of the extracellular NMN label was present as extracellular NR.

Human TDO2 substrate and product structures support oxidative conversion of L-tryptophan and oxygen to N-formylkynurenine.

In the human TDO2 substrate complex, molecular oxygen was coordinated to the heme iron next to the L-tryptophan substrate.

Crystallography and metal characterization identified iron in the active site of human HAAO, with spectroscopic behavior consistent with the ferrous preparation before air oxidation.

Human HAAO expressed in HEK-293 cells was enzymatically active toward 3-hydroxyanthranilate, with an apparent substrate Km near 2 micromolar in the study of the quinolinate-producing pathway step.

Human QPRT converts quinolinate and PRPP toward nicotinic acid mononucleotide; the human enzyme structures resolve reactant quinolinate and product NaMN complexes.

Human SIRT2 deacetylated monoacetylated histone peptides in the NAD-consuming reaction producing nicotinamide and O-acetyl-ADP-ribose.

Human CD38 hydrolyzes NAD+ to free ADP-ribose and nicotinamide.

Human CD38 produces cyclic ADP-ribose as a low-efficiency branch of NAD+ cleavage.

Human CD38 also hydrolyzes cyclic ADP-ribose to ADP-ribose.

Extracellular cyclic ADP-ribose generated by human CD38-expressing COS1 cells was detected by calcium release from sea-urchin egg microsomes.

Intracellular free ADP-ribose gated calcium-permeable currents in HEK293 cells expressing human TRPM2/LTRPC2.

PARP1 with HPF1 and NAD+ ADP-ribosylated histone H3 at serines 10 and 28 in reconstituted assays.

PARP2 combined with HPF1 supported serine ADP-ribosylation of histones in NAD+-containing reconstitutions.

HPF1-null U2OS cells showed near-loss of histone serine ADP-ribosylation after hydrogen-peroxide-induced DNA damage.

Purified human SARM1 TIR domain cleaved NAD+, producing ADP-ribose and nicotinamide as major products.

Human SARM1 TIR-domain NAD+ cleavage also generated cyclic ADP-ribose as a minor product.

Nicotinamide inhibited purified human SARM1 TIR NADase activity, with an assay IC50 of 43.8 micromolar.

The human SARM1 TIR E642A mutant failed to cleave NAD+ in the cell-free NADase assay.

After axotomy of Sarm1-null mouse DRG neurons, re-expression of active human SARM1 restored rapid axonal NAD+ depletion, whereas E642A did not.

NNMT transfers a methyl group from SAM to nicotinamide, yielding N1-methylnicotinamide and S-adenosylhomocysteine.

NNMT overexpression raised cellular SAH relative to GFP or inactive-NNMT controls in the tested human cancer-cell models.

At standard 100 micromolar medium methionine, NNMT overexpression changed SAM by less than 1.5-fold despite increased SAH.

In 769P cells cultured with 10 micromolar methionine, NNMT overexpression significantly lowered SAM relative to control cells.

At 10–20 micromolar medium methionine, NNMT-overexpressing 769P cells had reduced methylation of several histone lysine marks compared with controls.

After 24 hours of labeled N1-methylnicotinamide exposure, cancer-cell tracing did not detect conversion to other labeled metabolites.

Purified full-length human NADK catalyzed NADP+ production from NAD+ in a coupled assay supplied with 5 mM MgATP.

Cryo-EM resolved full-length human NADK as a tetramer with active sites spanning adjacent monomers.

The recombinant human NADK study did not detect phosphorylation of nicotinic acid adenine dinucleotide (NAAD).

Purified human NADK2 Δ62 converted NAD+ to NADP+ with ATP in MgCl2-containing reactions; TLC also detected ADP formation.

Purified human NADK2 Δ62 also supported NADP+ formation using inorganic polyphosphate preparations as phosphate donors.

The tested NADH kinase activity of purified human NADK2 Δ62 was about 10% of its NAD+ kinase activity.

Full-length human NADK2 localized to mitochondria in HEK293A cells; deletion of its first 62 residues disrupted that localization.

NADK2 knockdown reduced measured mitochondrial-fraction NAD kinase activity to 47% of control in HEK293A cells.

Three days after NADK2 knockdown, HEK293A intracellular ROS-probe signals increased with and without the tested menadione challenge.

The same short NADK2-knockdown experiment did not detect reduced HEK293A viability, including in the tested menadione condition.

Patient fibroblasts bearing a pathogenic NADK2 alteration had reduced mitochondrial NADP(H).

Dienoyl-CoA reductase activity was deficient in lysates from the NADK2 patient fibroblasts.

Transfection with functional NADK2 rescued deficient DECR activity in the patient-cell experiments.

Structural analysis of mammalian NNT supported coupling of NADH-to-NADP+ hydride transfer to proton translocation across the mitochondrial membrane.

In the cardiac pathological-workload study, reverse-mode Nnt consumed NADPH while supporting NADH and ATP production.

Re-expression of SLC25A51 restored exogenous NAD+ uptake into mitochondria isolated from SLC25A51-deficient cells.

SLC25A51 loss reduced mitochondrial NAD+ availability in the tested human cell models.

SLC25A51 loss did not reduce whole-cell NAD+ content in the comparisons that showed mitochondrial depletion.

The cohort also included homozygous KYNU p.V57Efs21 and compound-heterozygous p.Y156/p.F349Kfs*4 patients with reduced circulating NAD and multiple malformations.