Nicotinamide

evidence_access

Primary abstract

experimental_model

Human phase-1 study.

limitations

Not a definitive kidney-protection trial or proof that every blocked de novo step can be clinically bypassed.

nutrient_topic

Tryptophan collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Tryptophan

plain_language

An alternate NAD precursor reached downstream metabolism in a human pilot.

primary_references

De novo NAD+ biosynthetic impairment in acute kidney injury in humans. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30127395/ · DOI 10.1038/s41591-018-0138-z

Tryptophan: transport, protein synthesis, neuroactive metabolites, NAD and microbial pathways (2026-09-19) · lines 266–272

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human phase-1 study. · source_derived_draft · unverified_draft

## tryptophan-nam-clinical An alternate NAD precursor reached downstream metabolism in a human pilot. A phase-1 placebo-controlled oral nicotinamide study showed dose-related increases in circulating NAD metabolites and an exploratory association with less acute kidney injury. Model: Human phase-1 study. Limitations: Not a definitive kidney-protection trial or proof that every blocked de novo step can be clinically bypassed. Evidence access: Primary abstract De novo NAD+ biosynthetic impairment in acute kidney injury in humans. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30127395/ · DOI 10.1038/s41591-018-0138-z

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text, Figure 2

experimental_model

Mouse Ace2 loss and DSS challenge.

limitations

Does not establish identical effects for nicotinic acid or human inflammatory bowel disease.

nutrient_topic

Tryptophan collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Tryptophan

plain_language

A downstream vitamin B3 form bypassed part of the disturbed pathway.

primary_references

ACE2 links amino acid malnutrition to microbial ecology and intestinal inflammation. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22837003/ · DOI 10.1038/nature11228

trigger_kind

machinery_impairment Imported condition classification; unverified.

Tryptophan: transport, protein synthesis, neuroactive metabolites, NAD and microbial pathways (2026-09-19) · lines 90–96

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse Ace2 loss and DSS challenge. · source_derived_draft · unverified_draft

## tryptophan-nam-rescue A downstream vitamin B3 form bypassed part of the disturbed pathway. Nicotinamide supplementation markedly alleviated colitis and diarrhea in Ace2-deficient mice. Model: Mouse Ace2 loss and DSS challenge. Limitations: Does not establish identical effects for nicotinic acid or human inflammatory bowel disease. Evidence access: Primary full text, Figure 2 ACE2 links amino acid malnutrition to microbial ecology and intestinal inflammation. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22837003/ · DOI 10.1038/nature11228

cross_nutrient

false

evidence_span

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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

evidence_span

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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

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

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

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

evidence_access

Primary full text

experimental_model

Mouse circulating/tissue stable-isotope flux measurements.

limitations

Does not imply that all tissues lack de novo synthesis or that liver is the only contributor under every condition.

nutrient_topic

NAD+ collection; molecular form, preparation, species, exposure and manipulation remain explicit. · NAD+

plain_language

One organ can help supply another with recycled vitamin material.

primary_references

Quantitative Analysis of NAD Synthesis-Breakdown Fluxes. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29685734/ · DOI 10.1016/j.cmet.2018.03.018

NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 188–194

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse circulating/tissue stable-isotope flux measurements. · source_derived_draft · unverified_draft

## nad-plus-liver-nam-export One organ can help supply another with recycled vitamin material. Mouse tracer experiments identified liver conversion of tryptophan to NAD followed by nicotinamide release to support other tissues. Model: Mouse circulating/tissue stable-isotope flux measurements. Limitations: Does not imply that all tissues lack de novo synthesis or that liver is the only contributor under every condition. Evidence access: Primary full text Quantitative Analysis of NAD Synthesis-Breakdown Fluxes. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29685734/ · DOI 10.1016/j.cmet.2018.03.018

evidence_access

Primary full text

experimental_model

Mouse oral versus intravenous isotope-labeled precursor administration.

limitations

This study tests NR/NMN, not intact NAD infusion; it does not establish an optimal human route.

nutrient_topic

NAD+ collection; molecular form, preparation, species, exposure and manipulation remain explicit. · NAD+

plain_language

Route of administration changes which molecules tissues encounter.

primary_references

Quantitative Analysis of NAD Synthesis-Breakdown Fluxes. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29685734/ · DOI 10.1016/j.cmet.2018.03.018

NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 196–202

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse oral versus intravenous isotope-labeled precursor administration. · source_derived_draft · unverified_draft

## nad-plus-oral-versus-iv-precursors Route of administration changes which molecules tissues encounter. In mouse tracer experiments, oral NR and NMN were largely metabolized to nicotinamide, whereas intravenous administration delivered intact precursors to multiple tissues. Model: Mouse oral versus intravenous isotope-labeled precursor administration. Limitations: This study tests NR/NMN, not intact NAD infusion; it does not establish an optimal human route. Evidence access: Primary full text Quantitative Analysis of NAD Synthesis-Breakdown Fluxes. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29685734/ · DOI 10.1016/j.cmet.2018.03.018

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

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

evidence_access

Primary full text

experimental_model

Low-dose time course; 5 micromolar used in dependency experiments.

limitations

Whole-cell NAD is not a measurement of every subcellular pool.

nutrient_topic

Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol

plain_language

Initial consumption and later replenishment are separate phases.

primary_references

A human tRNA synthetase is a potent PARP1-activating effector target for resveratrol. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25533949/ · DOI 10.1038/nature14028

Resveratrol: metabolites, target selectivity and cross-nutrient mechanisms (2026-09-19) · lines 310–316

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Low-dose time course; 5 micromolar used in dependency experiments. · source_derived_draft · unverified_draft

## resveratrol-nad-timecourse Initial consumption and later replenishment are separate phases. In human HeLa cells, resveratrol initially reduced NAD with increased nicotinamide/ADP-ribose at 15 minutes; low concentrations raised NAD by one hour. Model: Low-dose time course; 5 micromolar used in dependency experiments. Limitations: Whole-cell NAD is not a measurement of every subcellular pool. Evidence access: Primary full text A human tRNA synthetase is a potent PARP1-activating effector target for resveratrol. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25533949/ · DOI 10.1038/nature14028

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text, mTOR results and Supplementary Figure 22 description

experimental_model

Mouse mTOR inhibition in vivo.

limitations

Rapamycin affects multiple cell types; no human dietary threshold established.

nutrient_topic

Tryptophan collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Tryptophan

plain_language

More precursor or downstream vitamin cannot replace every missing signal.

primary_references

ACE2 links amino acid malnutrition to microbial ecology and intestinal inflammation. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22837003/ · DOI 10.1038/nature11228

trigger_kind

machinery_impairment Imported condition classification; unverified.

Tryptophan: transport, protein synthesis, neuroactive metabolites, NAD and microbial pathways (2026-09-19) · lines 98–104

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse mTOR inhibition in vivo. · source_derived_draft · unverified_draft

## tryptophan-mtor-block-nam More precursor or downstream vitamin cannot replace every missing signal. Rapamycin reduced mouse intestinal antimicrobial peptides, and nicotinamide did not rescue that reduction. Model: Mouse mTOR inhibition in vivo. Limitations: Rapamycin affects multiple cell types; no human dietary threshold established. Evidence access: Primary full text, mTOR results and Supplementary Figure 22 description ACE2 links amino acid malnutrition to microbial ecology and intestinal inflammation. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22837003/ · DOI 10.1038/nature11228

evidence_access

Primary full text

experimental_model

Mouse biochemical, cellular and ecto-CD38 antibody experiments.

limitations

Not established clinical benefit from an over-the-counter CD38 inhibitor.

nutrient_topic

NAD+ collection; molecular form, preparation, species, exposure and manipulation remain explicit. · NAD+

plain_language

A precursor can be destroyed before a neighboring cell uses it.

primary_references

CD38 ecto-enzyme in immune cells is induced during aging and regulates NAD+ and NMN levels. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33199925/ · DOI 10.1038/s42255-020-00298-z

NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 116–122

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse biochemical, cellular and ecto-CD38 antibody experiments. · source_derived_draft · unverified_draft

## nad-plus-ecto-cd38-nmn A precursor can be destroyed before a neighboring cell uses it. The study linked extracellular CD38 enzymatic activity to NMN degradation and lower precursor availability; selective blockade of ecto-CD38 increased NAD+ in mouse experiments. Model: Mouse biochemical, cellular and ecto-CD38 antibody experiments. Limitations: Not established clinical benefit from an over-the-counter CD38 inhibitor. Evidence access: Primary full text CD38 ecto-enzyme in immune cells is induced during aging and regulates NAD+ and NMN levels. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33199925/ · DOI 10.1038/s42255-020-00298-z

evidence_access

Primary full text

experimental_model

Same 11-person human pilot.

limitations

Not a quantitative map of every tissue uptake route or evidence of rejuvenation.

nutrient_topic

NAD+ collection; molecular form, preparation, species, exposure and manipulation remain explicit. · NAD+

plain_language

Some infused material is broken down or excreted.

primary_references

A Pilot Study Investigating Changes in the Human Plasma and Urine NAD+ Metabolome During a 6 Hour Intravenous Infusion of NAD. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31572171/ · DOI 10.3389/fnagi.2019.00257

NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 292–298

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Same 11-person human pilot. · source_derived_draft · unverified_draft

## nad-plus-iv-metabolites Some infused material is broken down or excreted. The six-hour NAD+ infusion altered circulating breakdown products and urinary NAD/metabolite excretion, demonstrating substantial handling of administered material. Model: Same 11-person human pilot. Limitations: Not a quantitative map of every tissue uptake route or evidence of rejuvenation. Evidence access: Primary full text A Pilot Study Investigating Changes in the Human Plasma and Urine NAD+ Metabolome During a 6 Hour Intravenous Infusion of NAD. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31572171/ · DOI 10.3389/fnagi.2019.00257

evidence_access

Primary full text

experimental_model

E. coli PncA genetic experiments, mammalian cancer cells and xenografts.

limitations

PncA is bacterial; do not create a human nicotinamidase from this result.

nutrient_topic

NAD+ collection; molecular form, preparation, species, exposure and manipulation remain explicit. · NAD+

plain_language

Microbes can redirect one vitamin form into another route around a blocked enzyme.

primary_references

Bacteria Boost Mammalian Host NAD Metabolism by Engaging the Deamidated Biosynthesis Pathway. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32130883/ · DOI 10.1016/j.cmet.2020.02.001

NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 164–170

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · E. coli PncA genetic experiments, mammalian cancer cells and xenografts. · source_derived_draft · unverified_draft

## nad-plus-microbial-deamidation Microbes can redirect one vitamin form into another route around a blocked enzyme. Bacterial PncA converted nicotinamide to nicotinic acid, enabling an alternative deamidated NAD synthesis route in mammalian cells. Model: E. coli PncA genetic experiments, mammalian cancer cells and xenografts. Limitations: PncA is bacterial; do not create a human nicotinamidase from this result. Evidence access: Primary full text Bacteria Boost Mammalian Host NAD Metabolism by Engaging the Deamidated Biosynthesis Pathway. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32130883/ · DOI 10.1016/j.cmet.2020.02.001

evidence_access

Primary full text

experimental_model

Mouse isotope tracing and microbiota-depletion experiments.

limitations

Not a measured human conversion fraction or proof that all formulations use the same route.

nutrient_topic

NAD+ collection; molecular form, preparation, species, exposure and manipulation remain explicit. · NAD+

plain_language

An oral precursor may reach tissues through a microbially altered route.

primary_references

Bacteria Boost Mammalian Host NAD Metabolism by Engaging the Deamidated Biosynthesis Pathway. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32130883/ · DOI 10.1016/j.cmet.2020.02.001

NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 180–186

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse isotope tracing and microbiota-depletion experiments. · source_derived_draft · unverified_draft

## nad-plus-microbiota-oral-precursors An oral precursor may reach tissues through a microbially altered route. Stable-isotope tracing and microbiota depletion showed bacterial deamidation contributed substantially to tissue NAD increases after oral nicotinamide or NR in mice. Model: Mouse isotope tracing and microbiota-depletion experiments. Limitations: Not a measured human conversion fraction or proof that all formulations use the same route. Evidence access: Primary full text Bacteria Boost Mammalian Host NAD Metabolism by Engaging the Deamidated Biosynthesis Pathway. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32130883/ · DOI 10.1016/j.cmet.2020.02.001

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

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

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

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

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

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

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

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

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

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

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