Nicotinamide riboside

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Human cell add-back experiments.

limitations

Cell rescue is not established treatment for inherited NAXD disease.

nutrient_topic

L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine

plain_language

Two metabolic inputs partly bypassed a specific cellular vulnerability.

primary_references

Failure to repair damaged NAD(P)H blocks de novo serine synthesis in human cells. · 2025 · https://pubmed.ncbi.nlm.nih.gov/39789421/ · DOI 10.1186/s11658-024-00681-8

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 134–140

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cell add-back experiments. · source_derived_draft · unverified_draft

## l-serine-naxd-small-molecule-rescue Two metabolic inputs partly bypassed a specific cellular vulnerability. Nicotinamide riboside and inosine partly improved viability of galactose-grown NAXD-null HAP1 cells, with metabolomics suggesting different mechanisms involving serine synthesis. Model: Human cell add-back experiments. Limitations: Cell rescue is not established treatment for inherited NAXD disease. Evidence access: Primary full text Failure to repair damaged NAD(P)H blocks de novo serine synthesis in human cells. · 2025 · https://pubmed.ncbi.nlm.nih.gov/39789421/ · DOI 10.1186/s11658-024-00681-8

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

evidence_span

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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

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

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

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

access_level

full_text_and_supplement_review

compartment

Cardiac tissue / mitochondria

dose

400 mg/kg/day

duration

Figure 2 treatment timeline; exact intervention duration not independently resolved from narrative

endpoint

mouse-cardiac-fao

evidence_location

Figure 2M–O

experimental_model

Mouse two-hit HFpEF model: 60% fat-calorie diet plus L-NAME 0.5 g/L drinking water; additional intervention as stated

exposure

nicotinamide-riboside

limitations

Single primary study; not independently replicated here. Cardiac and recombinant findings do not establish pulmonary endothelial, viral-sepsis or ARDS effects. Mouse pharmacological exposure, not a human supplement efficacy or dose claim.

nutrient_topic

Topical cross-reference only; no inheritance of another actor's effects. · NAD+

organism

Mus musculus

plain_language

Nicotinamide riboside improved substrate-supported respiration in HFpEF mouse hearts.

primary_locator

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primary_references

https://doi.org/10.1038/s41467-026-70703-w

route

Oral gavage

sample_size

4 biological replicates

tissue_or_cell_type

Cardiac tissue and cardiomyocytes

DLAT: cardiac fatty-acid oxidation and mitochondrial glutathione evidence · lines 551–567

AI-assisted two-paper curation, 2026-09-20. Cardiac full-text/supplement review; CRC abstract only. No pulmonary endothelial validation. · supports · Mouse two-hit HFpEF model: 60% fat-calorie diet plus L-NAME 0.5 g/L drinking water; additional intervention as stated · source_derived_draft · unverified_draft

Nicotinamide riboside improved substrate-supported respiration in HFpEF mouse hearts. organism: Mus musculus tissue_or_cell_type: Cardiac tissue and cardiomyocytes experimental_model: Mouse two-hit HFpEF model: 60% fat-calorie diet plus L-NAME 0.5 g/L drinking water; additional intervention as stated compartment: Cardiac tissue / mitochondria dose: 400 mg/kg/day duration: Figure 2 treatment timeline; exact intervention duration not independently resolved from narrative route: Oral gavage primary_references: https://doi.org/10.1038/s41467-026-70703-w access_level: full_text_and_supplement_review evidence_location: Figure 2M–O endpoint: mouse-cardiac-fao exposure: nicotinamide-riboside limitations: Single primary study; not independently replicated here. Cardiac and recombinant findings do not establish pulmonary endothelial, viral-sepsis or ARDS effects. Mouse pharmacological exposure, not a human supplement efficacy or dose claim. primary_locator: [{"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 25, "text_sha256": "1814242d6194ed4e0b3ab78287e20f85b6bc243051183d0f24d9034c3a930257", "xml_element_id": null}, {"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 26, "text_sha256": "61dd26202087c725d9dc65345339778ed43192b3f765d05fa8a311a6e1944b34", "xml_element_id": "Par11"}, {"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 72, "text_sha256": "2b1ada63fe6c48d4296bbfb14a97940ac4a866b1d5171b0923851ec72f88ab15", "xml_element_id": "Par31"}] plain_language: Nicotinamide riboside improved substrate-supported respiration in HFpEF mouse hearts. sample_size: 4 biological replicates

access_level

full_text_and_supplement_review

compartment

Cardiac tissue / mitochondria

dose

400 mg/kg/day

duration

Figure 2 treatment timeline; exact intervention duration not independently resolved from narrative

endpoint

mouse-cardiac-diastolic-impairment

evidence_location

Supplementary Figure S6

experimental_model

Mouse two-hit HFpEF model: 60% fat-calorie diet plus L-NAME 0.5 g/L drinking water; additional intervention as stated

exposure

nicotinamide-riboside

limitations

Single primary study; not independently replicated here. Cardiac and recombinant findings do not establish pulmonary endothelial, viral-sepsis or ARDS effects. Systemic metabolic effects can contribute; no human efficacy inference.

nutrient_topic

Topical cross-reference only; no inheritance of another actor's effects. · NAD+

organism

Mus musculus

plain_language

Nicotinamide riboside improved the reported diastolic phenotype in the mouse HFpEF model.

primary_locator

[{"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 26, "text_sha256": "61dd26202087c725d9dc65345339778ed43192b3f765d05fa8a311a6e1944b34", "xml_element_id": "Par11"}, {"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 72, "text_sha256": "2b1ada63fe6c48d4296bbfb14a97940ac4a866b1d5171b0923851ec72f88ab15", "xml_element_id": "Par31"}]

primary_references

https://doi.org/10.1038/s41467-026-70703-w

route

Oral gavage

tissue_or_cell_type

Cardiac tissue and cardiomyocytes

DLAT: cardiac fatty-acid oxidation and mitochondrial glutathione evidence · lines 570–585

AI-assisted two-paper curation, 2026-09-20. Cardiac full-text/supplement review; CRC abstract only. No pulmonary endothelial validation. · supports · Mouse two-hit HFpEF model: 60% fat-calorie diet plus L-NAME 0.5 g/L drinking water; additional intervention as stated · source_derived_draft · unverified_draft

Nicotinamide riboside improved the reported diastolic phenotype in the mouse HFpEF model. organism: Mus musculus tissue_or_cell_type: Cardiac tissue and cardiomyocytes experimental_model: Mouse two-hit HFpEF model: 60% fat-calorie diet plus L-NAME 0.5 g/L drinking water; additional intervention as stated compartment: Cardiac tissue / mitochondria dose: 400 mg/kg/day duration: Figure 2 treatment timeline; exact intervention duration not independently resolved from narrative route: Oral gavage primary_references: https://doi.org/10.1038/s41467-026-70703-w access_level: full_text_and_supplement_review evidence_location: Supplementary Figure S6 endpoint: mouse-cardiac-diastolic-impairment exposure: nicotinamide-riboside limitations: Single primary study; not independently replicated here. Cardiac and recombinant findings do not establish pulmonary endothelial, viral-sepsis or ARDS effects. Systemic metabolic effects can contribute; no human efficacy inference. primary_locator: [{"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 26, "text_sha256": "61dd26202087c725d9dc65345339778ed43192b3f765d05fa8a311a6e1944b34", "xml_element_id": "Par11"}, {"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 72, "text_sha256": "2b1ada63fe6c48d4296bbfb14a97940ac4a866b1d5171b0923851ec72f88ab15", "xml_element_id": "Par31"}] plain_language: Nicotinamide riboside improved the reported diastolic phenotype in the mouse HFpEF model.

access_level

full_text_and_supplement_review

compartment

Cardiac tissue / mitochondria

dose

400 mg/kg/day

duration

Figure 2 treatment timeline; exact intervention duration not independently resolved from narrative

endpoint

mouse-hadha-acetylation

evidence_location

IP/immunoblot; Figure 2L

experimental_model

Mouse two-hit HFpEF model: 60% fat-calorie diet plus L-NAME 0.5 g/L drinking water; additional intervention as stated

exposure

nicotinamide-riboside

limitations

Single primary study; not independently replicated here. Cardiac and recombinant findings do not establish pulmonary endothelial, viral-sepsis or ARDS effects. The experiment does not establish selective direct NR action on HADHA or prove SIRT3 is the only mediator.

nutrient_topic

Topical cross-reference only; no inheritance of another actor's effects. · NAD+

organism

Mus musculus

plain_language

Nicotinamide riboside supplementation reduced HADHA acetylation in HFpEF mouse hearts.

primary_locator

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primary_references

https://doi.org/10.1038/s41467-026-70703-w

route

Oral gavage

sample_size

3 per group

tissue_or_cell_type

Cardiac tissue and cardiomyocytes

DLAT: cardiac fatty-acid oxidation and mitochondrial glutathione evidence · lines 532–548

AI-assisted two-paper curation, 2026-09-20. Cardiac full-text/supplement review; CRC abstract only. No pulmonary endothelial validation. · supports · Mouse two-hit HFpEF model: 60% fat-calorie diet plus L-NAME 0.5 g/L drinking water; additional intervention as stated · source_derived_draft · unverified_draft

Nicotinamide riboside supplementation reduced HADHA acetylation in HFpEF mouse hearts. organism: Mus musculus tissue_or_cell_type: Cardiac tissue and cardiomyocytes experimental_model: Mouse two-hit HFpEF model: 60% fat-calorie diet plus L-NAME 0.5 g/L drinking water; additional intervention as stated compartment: Cardiac tissue / mitochondria dose: 400 mg/kg/day duration: Figure 2 treatment timeline; exact intervention duration not independently resolved from narrative route: Oral gavage primary_references: https://doi.org/10.1038/s41467-026-70703-w access_level: full_text_and_supplement_review evidence_location: IP/immunoblot; Figure 2L endpoint: mouse-hadha-acetylation exposure: nicotinamide-riboside limitations: Single primary study; not independently replicated here. Cardiac and recombinant findings do not establish pulmonary endothelial, viral-sepsis or ARDS effects. The experiment does not establish selective direct NR action on HADHA or prove SIRT3 is the only mediator. primary_locator: [{"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 25, "text_sha256": "1814242d6194ed4e0b3ab78287e20f85b6bc243051183d0f24d9034c3a930257", "xml_element_id": null}, {"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 26, "text_sha256": "61dd26202087c725d9dc65345339778ed43192b3f765d05fa8a311a6e1944b34", "xml_element_id": "Par11"}, {"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 72, "text_sha256": "2b1ada63fe6c48d4296bbfb14a97940ac4a866b1d5171b0923851ec72f88ab15", "xml_element_id": "Par31"}] plain_language: Nicotinamide riboside supplementation reduced HADHA acetylation in HFpEF mouse hearts. sample_size: 3 per group

access_level

full_text_and_supplement_review

compartment

Cardiac tissue / mitochondria

dose

400 mg/kg/day

duration

Figure 2 treatment timeline; exact intervention duration not independently resolved from narrative

endpoint

mouse-cardiac-nad-pool

evidence_location

NAD+ assay kit; Figure 2I

experimental_model

Mouse two-hit HFpEF model: 60% fat-calorie diet plus L-NAME 0.5 g/L drinking water; additional intervention as stated

exposure

nicotinamide-riboside

limitations

Single primary study; not independently replicated here. Cardiac and recombinant findings do not establish pulmonary endothelial, viral-sepsis or ARDS effects.

nutrient_topic

Topical cross-reference only; no inheritance of another actor's effects. · NAD+

organism

Mus musculus

plain_language

Oral nicotinamide riboside increased the measured cardiac NAD+ pool in the two-hit HFpEF study.

primary_locator

[{"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 25, "text_sha256": "1814242d6194ed4e0b3ab78287e20f85b6bc243051183d0f24d9034c3a930257", "xml_element_id": null}, {"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 26, "text_sha256": "61dd26202087c725d9dc65345339778ed43192b3f765d05fa8a311a6e1944b34", "xml_element_id": "Par11"}, {"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 72, "text_sha256": "2b1ada63fe6c48d4296bbfb14a97940ac4a866b1d5171b0923851ec72f88ab15", "xml_element_id": "Par31"}]

primary_references

https://doi.org/10.1038/s41467-026-70703-w

route

Oral gavage

sample_size

6 per group

tissue_or_cell_type

Cardiac tissue and cardiomyocytes

DLAT: cardiac fatty-acid oxidation and mitochondrial glutathione evidence · lines 513–529

AI-assisted two-paper curation, 2026-09-20. Cardiac full-text/supplement review; CRC abstract only. No pulmonary endothelial validation. · supports · Mouse two-hit HFpEF model: 60% fat-calorie diet plus L-NAME 0.5 g/L drinking water; additional intervention as stated · source_derived_draft · unverified_draft

Oral nicotinamide riboside increased the measured cardiac NAD+ pool in the two-hit HFpEF study. organism: Mus musculus tissue_or_cell_type: Cardiac tissue and cardiomyocytes experimental_model: Mouse two-hit HFpEF model: 60% fat-calorie diet plus L-NAME 0.5 g/L drinking water; additional intervention as stated compartment: Cardiac tissue / mitochondria dose: 400 mg/kg/day duration: Figure 2 treatment timeline; exact intervention duration not independently resolved from narrative route: Oral gavage primary_references: https://doi.org/10.1038/s41467-026-70703-w access_level: full_text_and_supplement_review evidence_location: NAD+ assay kit; Figure 2I endpoint: mouse-cardiac-nad-pool exposure: nicotinamide-riboside limitations: Single primary study; not independently replicated here. Cardiac and recombinant findings do not establish pulmonary endothelial, viral-sepsis or ARDS effects. primary_locator: [{"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 25, "text_sha256": "1814242d6194ed4e0b3ab78287e20f85b6bc243051183d0f24d9034c3a930257", "xml_element_id": null}, {"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 26, "text_sha256": "61dd26202087c725d9dc65345339778ed43192b3f765d05fa8a311a6e1944b34", "xml_element_id": "Par11"}, {"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 72, "text_sha256": "2b1ada63fe6c48d4296bbfb14a97940ac4a866b1d5171b0923851ec72f88ab15", "xml_element_id": "Par31"}] plain_language: Oral nicotinamide riboside increased the measured cardiac NAD+ pool in the two-hit HFpEF study. sample_size: 6 per group

access_level

full_text_and_supplement_review

compartment

Mitochondria or cell lysate, depending on assay

dose

Compound concentration not established in reviewed text

duration

Treatment endpoint timing not established in reviewed text

endpoint

rat-cardiac-fao

evidence_location

Figure 2A–G

experimental_model

Pharmacological 3-TYP experiment; NR co-treatment where stated

exposure

nicotinamide-riboside

limitations

Single primary study; not independently replicated here. Cardiac and recombinant findings do not establish pulmonary endothelial, viral-sepsis or ARDS effects. The figure tests 3-TYP plus NR; do not mislabel it as an NR-alone dose-response experiment.

nutrient_topic

Topical cross-reference only; no inheritance of another actor's effects. · NAD+

organism

Rattus norvegicus host cells; construct species may be unspecified

plain_language

NR co-treatment opposed the impaired FAO-associated respiration in the 3-TYP rat-cell experiment.

primary_locator

[{"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 23, "text_sha256": "08f11746524e975c9e1a5e3d53de363a6762891bc05afffbd711f347867ac842", "xml_element_id": "Par10"}, {"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 25, "text_sha256": "1814242d6194ed4e0b3ab78287e20f85b6bc243051183d0f24d9034c3a930257", "xml_element_id": null}]

primary_references

https://doi.org/10.1038/s41467-026-70703-w

sample_size

4 respiratory replicates; 6 staining replicates

tissue_or_cell_type

Neonatal rat ventricular cardiomyocytes (NRVCMs)

DLAT: cardiac fatty-acid oxidation and mitochondrial glutathione evidence · lines 623–638

AI-assisted two-paper curation, 2026-09-20. Cardiac full-text/supplement review; CRC abstract only. No pulmonary endothelial validation. · supports · Pharmacological 3-TYP experiment; NR co-treatment where stated · source_derived_draft · unverified_draft

NR co-treatment opposed the impaired FAO-associated respiration in the 3-TYP rat-cell experiment. organism: Rattus norvegicus host cells; construct species may be unspecified tissue_or_cell_type: Neonatal rat ventricular cardiomyocytes (NRVCMs) experimental_model: Pharmacological 3-TYP experiment; NR co-treatment where stated compartment: Mitochondria or cell lysate, depending on assay dose: Compound concentration not established in reviewed text duration: Treatment endpoint timing not established in reviewed text primary_references: https://doi.org/10.1038/s41467-026-70703-w access_level: full_text_and_supplement_review evidence_location: Figure 2A–G endpoint: rat-cardiac-fao exposure: nicotinamide-riboside limitations: Single primary study; not independently replicated here. Cardiac and recombinant findings do not establish pulmonary endothelial, viral-sepsis or ARDS effects. The figure tests 3-TYP plus NR; do not mislabel it as an NR-alone dose-response experiment. primary_locator: [{"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 23, "text_sha256": "08f11746524e975c9e1a5e3d53de363a6762891bc05afffbd711f347867ac842", "xml_element_id": "Par10"}, {"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 25, "text_sha256": "1814242d6194ed4e0b3ab78287e20f85b6bc243051183d0f24d9034c3a930257", "xml_element_id": null}] plain_language: NR co-treatment opposed the impaired FAO-associated respiration in the 3-TYP rat-cell experiment. sample_size: 4 respiratory replicates; 6 staining replicates

evidence_access

Primary abstract

experimental_model

Human tumor-cell CD73 overexpression/silencing and FK866 experiments.

limitations

Mechanistic assignment is disputed by the later human recombinant-enzyme and knockout study. Primary abstract accessed here; direct catalytic attribution is retained as reported.

nutrient_topic

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

plain_language

One study found that CD73 helped cells use an outside NAD precursor.

primary_references

CD73 protein as a source of extracellular precursors for sustained NAD+ biosynthesis in FK866-treated tumor cells. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23880765/ · DOI 10.1074/jbc.M113.470435

NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 228–234

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human tumor-cell CD73 overexpression/silencing and FK866 experiments. · source_derived_draft · unverified_draft

## nad-plus-cd73-positive One study found that CD73 helped cells use an outside NAD precursor. CD73 silencing or pharmacological inhibition reduced NMN-supported survival after NAMPT inhibition in human tumor cells; the authors assigned CD73 a role in converting extracellular NMN to NR. Model: Human tumor-cell CD73 overexpression/silencing and FK866 experiments. Limitations: Mechanistic assignment is disputed by the later human recombinant-enzyme and knockout study. Primary abstract accessed here; direct catalytic attribution is retained as reported. Evidence access: Primary abstract CD73 protein as a source of extracellular precursors for sustained NAD+ biosynthesis in FK866-treated tumor cells. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23880765/ · DOI 10.1074/jbc.M113.470435

evidence_span

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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

evidence_access

Primary full text

experimental_model

Small nonrandomized retrospective clinical series.

limitations

Selection, infusion rate and clinic practices limit causal comparison; not efficacy evidence or an incidence estimate for all users.

nutrient_topic

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

plain_language

Infusion tolerability is a separate question from whether NAD biomarkers rise.

primary_references

Intravenous infusion of nicotinamide adenine dinucleotide (NAD+) versus nicotinamide riboside (NR): a retrospective tolerability pilot study in a real-world setting. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41704678/ · DOI 10.3389/fragi.2026.1652582

NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 300–306

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Small nonrandomized retrospective clinical series. · source_derived_draft · unverified_draft

## nad-plus-iv-tolerability Infusion tolerability is a separate question from whether NAD biomarkers rise. A retrospective commercial-clinic series compared six clients receiving 500 mg IV NAD+ with eight receiving 500 mg IV NR over four-day loading protocols; NAD recipients reported gastrointestinal symptoms, chest pressure or elevated heart rate and required longer infusions. Model: Small nonrandomized retrospective clinical series. Limitations: Selection, infusion rate and clinic practices limit causal comparison; not efficacy evidence or an incidence estimate for all users. Evidence access: Primary full text Intravenous infusion of nicotinamide adenine dinucleotide (NAD+) versus nicotinamide riboside (NR): a retrospective tolerability pilot study in a real-world setting. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41704678/ · DOI 10.3389/fragi.2026.1652582

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

evidence_span

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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

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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

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

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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

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

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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

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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

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

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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