NMN

evidence_access

Primary full text

experimental_model

Ten-week randomized trial in postmenopausal women with prediabetes; clamp and muscle signaling measurements.

limitations

Small defined population, not proof of longevity, benefit in healthy adults or a proven NAD mediator.

nutrient_topic

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

plain_language

A specific physiological improvement can occur without a measured rise in total muscle NAD.

primary_references

Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33888596/ · DOI 10.1126/science.abe9985

NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 340–346

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Ten-week randomized trial in postmenopausal women with prediabetes; clamp and muscle signaling measurements. · source_derived_draft · unverified_draft

## nad-plus-nmn-clamp A specific physiological improvement can occur without a measured rise in total muscle NAD. The same NMN trial increased insulin-stimulated glucose disposal and muscle insulin signaling relative to baseline, while placebo did not; the study did not demonstrate broad improvement in all metabolic endpoints. Model: Ten-week randomized trial in postmenopausal women with prediabetes; clamp and muscle signaling measurements. Limitations: Small defined population, not proof of longevity, benefit in healthy adults or a proven NAD mediator. Evidence access: Primary full text Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33888596/ · DOI 10.1126/science.abe9985

availability_state

biomarker_context Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Randomized double-blind trial; 13 NMN and 12 placebo; biopsies and metabolomics.

limitations

Catabolites suggest turnover but are not isotope-measured flux; total biopsy NAD can miss small subcellular pools.

nutrient_topic

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

plain_language

A blood-cell response did not mean measured muscle NAD rose.

primary_references

Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33888596/ · DOI 10.1126/science.abe9985

trigger_kind

biomarker_context Imported condition classification; unverified.

NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 332–338

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Randomized double-blind trial; 13 NMN and 12 placebo; biopsies and metabolomics. · source_derived_draft · unverified_draft

## nad-plus-nmn-muscle-versus-blood A blood-cell response did not mean measured muscle NAD rose. In 25 postmenopausal women with prediabetes and overweight/obesity, 250 mg/day NMN for ten weeks increased basal PBMC NAD but did not increase measured muscle NAD; muscle NAD-related catabolites increased. Model: Randomized double-blind trial; 13 NMN and 12 placebo; biopsies and metabolomics. Limitations: Catabolites suggest turnover but are not isotope-measured flux; total biopsy NAD can miss small subcellular pools. Evidence access: Primary full text Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33888596/ · DOI 10.1126/science.abe9985

evidence_access

Primary full text

experimental_model

Drosophila-domain ITC and structural experiments.

limitations

The binding affinity is for a fly domain, not a full-length human protein or a human toxicity threshold.

nutrient_topic

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

plain_language

The activating precursor has a directly measured binding site.

primary_references

SARM1 is a metabolic sensor activated by an increased NMN/NAD+ ratio to trigger axon degeneration. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33657413/ · DOI 10.1016/j.neuron.2021.02.009

NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 84–90

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Drosophila-domain ITC and structural experiments. · source_derived_draft · unverified_draft

## nad-plus-sarm-nmn-binding The activating precursor has a directly measured binding site. NMN bound the purified Drosophila SARM1 ARM domain at approximately 6.39 micromolar dissociation constant, with one ligand per domain. Model: Drosophila-domain ITC and structural experiments. Limitations: The binding affinity is for a fly domain, not a full-length human protein or a human toxicity threshold. Evidence access: Primary full text SARM1 is a metabolic sensor activated by an increased NMN/NAD+ ratio to trigger axon degeneration. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33657413/ · DOI 10.1016/j.neuron.2021.02.009

evidence_access

Primary full text

experimental_model

Purified human construct; NMR activity assays and cell experiments.

limitations

NAD+ is also the catalytic substrate, so activity cannot be inferred from ratio alone across all conditions. This does not show oral NMN causes nerve injury.

nutrient_topic

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

plain_language

The balance between a precursor and finished NAD can activate a destructive feedback loop.

primary_references

SARM1 is a metabolic sensor activated by an increased NMN/NAD+ ratio to trigger axon degeneration. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33657413/ · DOI 10.1016/j.neuron.2021.02.009

NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 76–82

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified human construct; NMR activity assays and cell experiments. · source_derived_draft · unverified_draft

## nad-plus-sarm-ratio The balance between a precursor and finished NAD can activate a destructive feedback loop. Increasing NMN relative to NAD+ increased NADase activity of purified human SARM1 residues 28–724, which retain ARM, SAM and TIR domains but lack the mitochondrial targeting sequence. Model: Purified human construct; NMR activity assays and cell experiments. Limitations: NAD+ is also the catalytic substrate, so activity cannot be inferred from ratio alone across all conditions. This does not show oral NMN causes nerve injury. Evidence access: Primary full text SARM1 is a metabolic sensor activated by an increased NMN/NAD+ ratio to trigger axon degeneration. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33657413/ · DOI 10.1016/j.neuron.2021.02.009

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_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

cross_nutrient

Adipose tissue insulin sensitivity (parallel_null_endpoint)

evidence_span

{"source_cache": "artifacts/niacin-clinical-sources/yoshino2021.txt", "locator": "Primary full report; exact character range, zero-based and end-exclusive", "file_sha256": "e4999dc5b9d3392d8180280727c424044b35249bb24c999c3bc863cd23e6c856", "start_char": 6120, "end_char": 7140, "text_sha256": "152262160f005f7aac5e078287acca1db556d35a8645d8892492723992dec2dc"}

experimental_model

Randomized double-blind trial; 25 overweight or obese postmenopausal women with prediabetes completed

exposure

NMN 250 mg/day for 10 weeks; 13 NMN and 12 placebo participants

limitations

Small selected female cohort. Tissue NAD concentration, NAD turnover and clinical outcomes differ. No lifespan or diabetes-prevention endpoint. Positive muscle findings do not establish whole-body or cross-population benefit.

nutrient_topic

Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)

organism

Homo sapiens

plain_language

The muscle result did not extend to all insulin-responsive organs or to a general metabolic improvement.

primary_references

[nia-clin-yoshino2021] Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. (2021). https://pubmed.ncbi.nlm.nih.gov/33888596/ DOI: 10.1126/science.abe9985

tissue_or_cell_type

Skeletal muscle, PBMCs, liver and adipose insulin sensitivity

Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 1529–1541

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized double-blind trial; 25 overweight or obese postmenopausal women with prediabetes completed · source_derived_draft · unverified_draft

### nia-clin-nmn-liver-insulin The NMN trial did not find improved hepatic or adipose tissue insulin sensitivity; fasting metabolic measures, body composition and liver fat were also unchanged. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The muscle result did not extend to all insulin-responsive organs or to a general metabolic improvement. organism: Homo sapiens tissue_or_cell_type: Skeletal muscle, PBMCs, liver and adipose insulin sensitivity experimental_model: Randomized double-blind trial; 25 overweight or obese postmenopausal women with prediabetes completed limitations: Small selected female cohort. Tissue NAD concentration, NAD turnover and clinical outcomes differ. No lifespan or diabetes-prevention endpoint. Positive muscle findings do not establish whole-body or cross-population benefit. exposure: NMN 250 mg/day for 10 weeks; 13 NMN and 12 placebo participants cross_nutrient: Adipose tissue insulin sensitivity (parallel_null_endpoint) evidence_span: {"source_cache": "artifacts/niacin-clinical-sources/yoshino2021.txt", "locator": "Primary full report; exact character range, zero-based and end-exclusive", "file_sha256": "e4999dc5b9d3392d8180280727c424044b35249bb24c999c3bc863cd23e6c856", "start_char": 6120, "end_char": 7140, "text_sha256": "152262160f005f7aac5e078287acca1db556d35a8645d8892492723992dec2dc"} [nia-clin-yoshino2021] Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. (2021). https://pubmed.ncbi.nlm.nih.gov/33888596/ DOI: 10.1126/science.abe9985

cross_nutrient

Insulin (test_signal)

evidence_span

{"source_cache": "artifacts/niacin-clinical-sources/yoshino2021.txt", "locator": "Primary full report; exact character range, zero-based and end-exclusive", "file_sha256": "e4999dc5b9d3392d8180280727c424044b35249bb24c999c3bc863cd23e6c856", "start_char": 6120, "end_char": 7140, "text_sha256": "152262160f005f7aac5e078287acca1db556d35a8645d8892492723992dec2dc"}

experimental_model

Randomized double-blind trial; 25 overweight or obese postmenopausal women with prediabetes completed

exposure

NMN 250 mg/day for 10 weeks; 13 NMN and 12 placebo participants

limitations

Small selected female cohort. Tissue NAD concentration, NAD turnover and clinical outcomes differ. No lifespan or diabetes-prevention endpoint. Positive muscle findings do not establish whole-body or cross-population benefit.

nutrient_topic

Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)

organism

Homo sapiens

plain_language

In this small group of women, muscle responded better to insulin during the clamp test.

primary_references

[nia-clin-yoshino2021] Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. (2021). https://pubmed.ncbi.nlm.nih.gov/33888596/ DOI: 10.1126/science.abe9985

tissue_or_cell_type

Skeletal muscle, PBMCs, liver and adipose insulin sensitivity

Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 1487–1499

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized double-blind trial; 25 overweight or obese postmenopausal women with prediabetes completed · source_derived_draft · unverified_draft

### nia-clin-nmn-muscle-insulin Insulin-stimulated glucose disposal per kg fat-free mass increased by 25±7% after ten weeks of NMN, while the placebo group showed no corresponding change. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: In this small group of women, muscle responded better to insulin during the clamp test. organism: Homo sapiens tissue_or_cell_type: Skeletal muscle, PBMCs, liver and adipose insulin sensitivity experimental_model: Randomized double-blind trial; 25 overweight or obese postmenopausal women with prediabetes completed limitations: Small selected female cohort. Tissue NAD concentration, NAD turnover and clinical outcomes differ. No lifespan or diabetes-prevention endpoint. Positive muscle findings do not establish whole-body or cross-population benefit. exposure: NMN 250 mg/day for 10 weeks; 13 NMN and 12 placebo participants cross_nutrient: Insulin (test_signal) evidence_span: {"source_cache": "artifacts/niacin-clinical-sources/yoshino2021.txt", "locator": "Primary full report; exact character range, zero-based and end-exclusive", "file_sha256": "e4999dc5b9d3392d8180280727c424044b35249bb24c999c3bc863cd23e6c856", "start_char": 6120, "end_char": 7140, "text_sha256": "152262160f005f7aac5e078287acca1db556d35a8645d8892492723992dec2dc"} [nia-clin-yoshino2021] Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. (2021). https://pubmed.ncbi.nlm.nih.gov/33888596/ DOI: 10.1126/science.abe9985

cross_nutrient

Nicotinamide adenine dinucleotide, oxidized (coenzyme); PBMC NAD+ content (separate_compartment_marker); N1-methylnicotinamide (muscle_metabolite)

evidence_span

{"source_cache": "artifacts/niacin-clinical-sources/yoshino2021.txt", "locator": "Primary full report; exact character range, zero-based and end-exclusive", "file_sha256": "e4999dc5b9d3392d8180280727c424044b35249bb24c999c3bc863cd23e6c856", "start_char": 4842, "end_char": 6119, "text_sha256": "bb73c5ac9d2ac503143ede8627aaa6be34763fdd501bf48a32528a332b89016c"}

experimental_model

Randomized double-blind trial; 25 overweight or obese postmenopausal women with prediabetes completed

exposure

NMN 250 mg/day for 10 weeks; 13 NMN and 12 placebo participants

limitations

Small selected female cohort. Tissue NAD concentration, NAD turnover and clinical outcomes differ. No lifespan or diabetes-prevention endpoint. Positive muscle findings do not establish whole-body or cross-population benefit.

nutrient_topic

Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)

organism

Homo sapiens

plain_language

More NAD-related activity did not necessarily mean a larger standing NAD pool in muscle.

primary_references

[nia-clin-yoshino2021] Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. (2021). https://pubmed.ncbi.nlm.nih.gov/33888596/ DOI: 10.1126/science.abe9985

tissue_or_cell_type

Skeletal muscle, PBMCs, liver and adipose insulin sensitivity

Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 1515–1527

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized double-blind trial; 25 overweight or obese postmenopausal women with prediabetes completed · source_derived_draft · unverified_draft

### nia-clin-nmn-muscle-nad Muscle NAD+ content did not rise after NMN even though PBMC NAD+ and muscle methylated niacin metabolites increased; authors interpreted the latter as consistent with increased turnover. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: More NAD-related activity did not necessarily mean a larger standing NAD pool in muscle. organism: Homo sapiens tissue_or_cell_type: Skeletal muscle, PBMCs, liver and adipose insulin sensitivity experimental_model: Randomized double-blind trial; 25 overweight or obese postmenopausal women with prediabetes completed limitations: Small selected female cohort. Tissue NAD concentration, NAD turnover and clinical outcomes differ. No lifespan or diabetes-prevention endpoint. Positive muscle findings do not establish whole-body or cross-population benefit. exposure: NMN 250 mg/day for 10 weeks; 13 NMN and 12 placebo participants cross_nutrient: Nicotinamide adenine dinucleotide, oxidized (coenzyme); PBMC NAD+ content (separate_compartment_marker); N1-methylnicotinamide (muscle_metabolite) evidence_span: {"source_cache": "artifacts/niacin-clinical-sources/yoshino2021.txt", "locator": "Primary full report; exact character range, zero-based and end-exclusive", "file_sha256": "e4999dc5b9d3392d8180280727c424044b35249bb24c999c3bc863cd23e6c856", "start_char": 4842, "end_char": 6119, "text_sha256": "bb73c5ac9d2ac503143ede8627aaa6be34763fdd501bf48a32528a332b89016c"} [nia-clin-yoshino2021] Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. (2021). https://pubmed.ncbi.nlm.nih.gov/33888596/ DOI: 10.1126/science.abe9985

cross_nutrient

Insulin (stimulus)

evidence_span

{"source_cache": "artifacts/niacin-clinical-sources/yoshino2021.txt", "locator": "Primary full report; exact character range, zero-based and end-exclusive", "file_sha256": "e4999dc5b9d3392d8180280727c424044b35249bb24c999c3bc863cd23e6c856", "start_char": 7141, "end_char": 7815, "text_sha256": "31871685ed5bb9ceb845b035d50807218311c0fad543f690e5ab924ba9872d0d"}

experimental_model

Randomized double-blind trial; 25 overweight or obese postmenopausal women with prediabetes completed

exposure

NMN 250 mg/day for 10 weeks; 13 NMN and 12 placebo participants

limitations

Small selected female cohort. Tissue NAD concentration, NAD turnover and clinical outcomes differ. No lifespan or diabetes-prevention endpoint. Positive muscle findings do not establish whole-body or cross-population benefit.

nutrient_topic

Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)

organism

Homo sapiens

plain_language

The muscle response was accompanied by changes in insulin-signaling proteins.

primary_references

[nia-clin-yoshino2021] Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. (2021). https://pubmed.ncbi.nlm.nih.gov/33888596/ DOI: 10.1126/science.abe9985

tissue_or_cell_type

Skeletal muscle, PBMCs, liver and adipose insulin sensitivity

Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 1501–1513

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized double-blind trial; 25 overweight or obese postmenopausal women with prediabetes completed · source_derived_draft · unverified_draft

### nia-clin-nmn-muscle-signal Muscle insulin-stimulated AKT and mTOR phosphorylation and total abundance increased after NMN but not placebo. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The muscle response was accompanied by changes in insulin-signaling proteins. organism: Homo sapiens tissue_or_cell_type: Skeletal muscle, PBMCs, liver and adipose insulin sensitivity experimental_model: Randomized double-blind trial; 25 overweight or obese postmenopausal women with prediabetes completed limitations: Small selected female cohort. Tissue NAD concentration, NAD turnover and clinical outcomes differ. No lifespan or diabetes-prevention endpoint. Positive muscle findings do not establish whole-body or cross-population benefit. exposure: NMN 250 mg/day for 10 weeks; 13 NMN and 12 placebo participants cross_nutrient: Insulin (stimulus) evidence_span: {"source_cache": "artifacts/niacin-clinical-sources/yoshino2021.txt", "locator": "Primary full report; exact character range, zero-based and end-exclusive", "file_sha256": "e4999dc5b9d3392d8180280727c424044b35249bb24c999c3bc863cd23e6c856", "start_char": 7141, "end_char": 7815, "text_sha256": "31871685ed5bb9ceb845b035d50807218311c0fad543f690e5ab924ba9872d0d"} [nia-clin-yoshino2021] Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. (2021). https://pubmed.ncbi.nlm.nih.gov/33888596/ DOI: 10.1126/science.abe9985

evidence_access

Primary full text

experimental_model

Human recombinant enzyme; biochemical substrate assays.

limitations

Do not erase the earlier cellular result. Preparation, assay sensitivity and indirect cellular effects require reconciliation.

nutrient_topic

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

plain_language

A later direct assay challenged the proposed precursor-processing enzyme.

primary_references

Extracellular NAD+ enhances PARP-dependent DNA repair capacity independently of CD73 activity. · 2020 · https://pubmed.ncbi.nlm.nih.gov/31959836/ · DOI 10.1038/s41598-020-57506-9

NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 236–242

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human recombinant enzyme; biochemical substrate assays. · source_derived_draft · unverified_draft

## nad-plus-cd73-negative A later direct assay challenged the proposed precursor-processing enzyme. Recombinant human CD73 did not process NAD+ and processed NMN poorly in the reported biochemical assays. Model: Human recombinant enzyme; biochemical substrate assays. Limitations: Do not erase the earlier cellular result. Preparation, assay sensitivity and indirect cellular effects require reconciliation. Evidence access: Primary full text Extracellular NAD+ enhances PARP-dependent DNA repair capacity independently of CD73 activity. · 2020 · https://pubmed.ncbi.nlm.nih.gov/31959836/ · DOI 10.1038/s41598-020-57506-9

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_span

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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

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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_access

Primary full text

experimental_model

Human cancer-cell CRISPR knockout and precursor supplementation.

limitations

Does not identify a universal alternative uptake route or prove intact NAD crossed the plasma membrane.

nutrient_topic

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

plain_language

Cells could still use outside precursor material without CD73.

primary_references

Extracellular NAD+ enhances PARP-dependent DNA repair capacity independently of CD73 activity. · 2020 · https://pubmed.ncbi.nlm.nih.gov/31959836/ · DOI 10.1038/s41598-020-57506-9

NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 244–250

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cancer-cell CRISPR knockout and precursor supplementation. · source_derived_draft · unverified_draft

## nad-plus-cd73-knockout Cells could still use outside precursor material without CD73. CD73 knockout did not prevent human cancer cells from using extracellular NAD+ or NMN to restore intracellular NAD+ under the tested conditions. Model: Human cancer-cell CRISPR knockout and precursor supplementation. Limitations: Does not identify a universal alternative uptake route or prove intact NAD crossed the plasma membrane. Evidence access: Primary full text Extracellular NAD+ enhances PARP-dependent DNA repair capacity independently of CD73 activity. · 2020 · https://pubmed.ncbi.nlm.nih.gov/31959836/ · DOI 10.1038/s41598-020-57506-9

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

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Mouse shRNA and enzyme re-expression experiments.

limitations

PARP activity is not a direct measurement of all nuclear NAD-dependent reactions.

nutrient_topic

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

plain_language

DNA-associated enzymes can depend on local NAD production.

primary_references

Metabolic regulation of transcription through compartmentalized NAD+ biosynthesis. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29748257/ · DOI 10.1126/science.aan5780

trigger_kind

machinery_impairment Imported condition classification; unverified.

NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 60–66

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse shRNA and enzyme re-expression experiments. · source_derived_draft · unverified_draft

## nad-plus-nmnat1-loss DNA-associated enzymes can depend on local NAD production. Nmnat1 knockdown reduced PARP1-mediated PARylation in mouse 3T3-L1 preadipocytes; catalytically active but not inactive NMNAT1 rescued the activity. Model: Mouse shRNA and enzyme re-expression experiments. Limitations: PARP activity is not a direct measurement of all nuclear NAD-dependent reactions. Evidence access: Primary full text Metabolic regulation of transcription through compartmentalized NAD+ biosynthesis. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29748257/ · DOI 10.1126/science.aan5780

evidence_access

Primary full text

experimental_model

Mouse preadipocyte differentiation, enzyme perturbations and compartment measurements.

limitations

Not evidence that human NMN supplements cause weight gain; enzyme location and differentiation state matter.

nutrient_topic

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

plain_language

Two compartments can compete for the same building material.

primary_references

Metabolic regulation of transcription through compartmentalized NAD+ biosynthesis. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29748257/ · DOI 10.1126/science.aan5780

NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 52–58

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse preadipocyte differentiation, enzyme perturbations and compartment measurements. · source_derived_draft · unverified_draft

## nad-plus-nmnat2-competition Two compartments can compete for the same building material. Adipogenic induction of cytoplasmic NMNAT2 in mouse 3T3-L1 cells competed with nuclear NMNAT1 for NMN and reduced nuclear NAD+ availability. Model: Mouse preadipocyte differentiation, enzyme perturbations and compartment measurements. Limitations: Not evidence that human NMN supplements cause weight gain; enzyme location and differentiation state matter. Evidence access: Primary full text Metabolic regulation of transcription through compartmentalized NAD+ biosynthesis. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29748257/ · DOI 10.1126/science.aan5780

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_access

Primary full text

experimental_model

Human MCF-7 cells with NAMPT inhibition, CD73 comparison and serum-containing medium; NMN/NR XRCC1 rescue is reported as data not shown.

limitations

Rescue depended on medium and incubation time; serum-free and heat-inactivated-serum conditions did not give the same early rescue. No proof of intact cellular NAD uptake or clinical benefit.

nutrient_topic

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

plain_language

Supplying precursor material restored part of a repair response in this model.

primary_references

Extracellular NAD+ enhances PARP-dependent DNA repair capacity independently of CD73 activity. · 2020 · https://pubmed.ncbi.nlm.nih.gov/31959836/ · DOI 10.1038/s41598-020-57506-9

NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 260–266

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human MCF-7 cells with NAMPT inhibition, CD73 comparison and serum-containing medium; NMN/NR XRCC1 rescue is reported as data not shown. · source_derived_draft · unverified_draft

## nad-plus-repair-precursor-rescue Supplying precursor material restored part of a repair response in this model. Extracellular NAD+ or NMN restored intracellular NAD availability, PAR-dependent signaling and XRCC1 recruitment in the tested NAD-depleted human cells independently of CD73 status. Model: Human MCF-7 cells with NAMPT inhibition, CD73 comparison and serum-containing medium; NMN/NR XRCC1 rescue is reported as data not shown. Limitations: Rescue depended on medium and incubation time; serum-free and heat-inactivated-serum conditions did not give the same early rescue. No proof of intact cellular NAD uptake or clinical benefit. Evidence access: Primary full text Extracellular NAD+ enhances PARP-dependent DNA repair capacity independently of CD73 activity. · 2020 · https://pubmed.ncbi.nlm.nih.gov/31959836/ · DOI 10.1038/s41598-020-57506-9

evidence_access

Primary full text

experimental_model

Drosophila-domain ITC and NMR competition.

limitations

Species/domain-specific affinity; separate from catalytic-site kinetics.

nutrient_topic

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

plain_language

NAD can help restrain the switch at a regulatory site while also being its substrate.

primary_references

SARM1 is a metabolic sensor activated by an increased NMN/NAD+ ratio to trigger axon degeneration. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33657413/ · DOI 10.1016/j.neuron.2021.02.009

NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 92–98

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Drosophila-domain ITC and NMR competition. · source_derived_draft · unverified_draft

## nad-plus-sarm-nad-binding NAD can help restrain the switch at a regulatory site while also being its substrate. NAD+ bound the same Drosophila SARM1 ARM-domain regulatory site with approximately 54.2 micromolar dissociation constant; competition assays supported opposing occupancy by NAD+ and NMN. Model: Drosophila-domain ITC and NMR competition. Limitations: Species/domain-specific affinity; separate from catalytic-site kinetics. Evidence access: Primary full text SARM1 is a metabolic sensor activated by an increased NMN/NAD+ ratio to trigger axon degeneration. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33657413/ · DOI 10.1016/j.neuron.2021.02.009

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

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

[{"source_cache": "artifacts/niacin-precursors-sources/nmrk2016.paragraphs.txt", "locator": "Normalized full-text paragraphs 30–30 (0-based)", "start_char": 33613, "end_char": 35106, "file_sha256": "fcbd5465aff51c9870d65fc9812edbad2cdf2af8bb16b6afb3170d7f0503178a", "text_sha256": "e43865f05c251c7fbb357b31c7968056ae1b58fb1d0f4e61216e5013cb928a41"}, {"source_cache": "artifacts/niacin-precursors-sources/nmrk2016.paragraphs.txt", "locator": "Normalized full-text paragraphs 48–48 (0-based)", "start_char": 46035, "end_char": 46419, "file_sha256": "fcbd5465aff51c9870d65fc9812edbad2cdf2af8bb16b6afb3170d7f0503178a", "text_sha256": "4261a1ca6a50f8b37fd569171c8a9111b9a5ee53b2504811a46cfb40badcb90c"}]

tissue_or_cell_type

NIH/3T3 fibroblasts

Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 395–407

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Murine NRK gain/loss of function in fibroblasts and primary hepatocytes; separate human HepG2 stable-isotope experiments · source_derived_draft · unverified_draft

### b3-pre-mouse-nrk1-nr Transient overexpression of active mouse NRK1 made NIH/3T3 fibroblasts responsive to nicotinamide riboside with increased cellular NAD+; the tested catalytically inactive kinase failed to support the response. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: NR utilization depended on active riboside kinase in this cell model. organism: Mus musculus tissue_or_cell_type: NIH/3T3 fibroblasts experimental_model: Murine NRK gain/loss of function in fibroblasts and primary hepatocytes; separate human HepG2 stable-isotope experiments limitations: Forced expression in mouse fibroblasts; not a human supplementation study. Basal NAD was unchanged by active kinase overexpression without NR. exposure: Transient kinase overexpression with 4 micrograms plasmid; NR 0.5 mM for 6 h under the stated default protocol; mutant comparator NRK1-D36A or NRK2-D35A. evidence_span: {"source_cache": "artifacts/niacin-precursors-sources/nmrk2016.paragraphs.txt", "locator": "Normalized full-text paragraphs 7–7 (0-based)", "start_char": 5559, "end_char": 7104, "file_sha256": "fcbd5465aff51c9870d65fc9812edbad2cdf2af8bb16b6afb3170d7f0503178a", "text_sha256": "ffb453285526cec1670cc565f0b57f3893b48aba7e5014f693f09ea75079348f"} supporting_evidence_spans: [{"source_cache": "artifacts/niacin-precursors-sources/nmrk2016.paragraphs.txt", "locator": "Normalized full-text paragraphs 30–30 (0-based)", "start_char": 33613, "end_char": 35106, "file_sha256": "fcbd5465aff51c9870d65fc9812edbad2cdf2af8bb16b6afb3170d7f0503178a", "text_sha256": "e43865f05c251c7fbb357b31c7968056ae1b58fb1d0f4e61216e5013cb928a41"}, {"source_cache": "artifacts/niacin-precursors-sources/nmrk2016.paragraphs.txt", "locator": "Normalized full-text paragraphs 48–48 (0-based)", "start_char": 46035, "end_char": 46419, "file_sha256": "fcbd5465aff51c9870d65fc9812edbad2cdf2af8bb16b6afb3170d7f0503178a", "text_sha256": "4261a1ca6a50f8b37fd569171c8a9111b9a5ee53b2504811a46cfb40badcb90c"}] [b3-pre-nmrk2016] NRK1 controls nicotinamide mononucleotide and nicotinamide riboside metabolism in mammalian cells. (2016). https://pubmed.ncbi.nlm.nih.gov/27725675/ DOI: 10.1038/ncomms13103

evidence_span

{"source_cache": "artifacts/niacin-precursors-sources/nmrk2016.paragraphs.txt", "locator": "Normalized full-text paragraphs 7–7 (0-based)", "start_char": 5559, "end_char": 7104, "file_sha256": "fcbd5465aff51c9870d65fc9812edbad2cdf2af8bb16b6afb3170d7f0503178a", "text_sha256": "ffb453285526cec1670cc565f0b57f3893b48aba7e5014f693f09ea75079348f"}

experimental_model

Murine NRK gain/loss of function in fibroblasts and primary hepatocytes; separate human HepG2 stable-isotope experiments

exposure

Transient kinase overexpression with 4 micrograms plasmid; NR 0.5 mM for 6 h under the stated default protocol; mutant comparator NRK1-D36A or NRK2-D35A.

limitations

Forced expression in mouse fibroblasts; not a human supplementation study. Basal NAD was unchanged by active kinase overexpression without NR.

nutrient_topic

Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)

organism

Mus musculus

plain_language

NR utilization depended on active riboside kinase in this cell model.

primary_references

[b3-pre-nmrk2016] NRK1 controls nicotinamide mononucleotide and nicotinamide riboside metabolism in mammalian cells. (2016). https://pubmed.ncbi.nlm.nih.gov/27725675/ DOI: 10.1038/ncomms13103

supporting_evidence_spans

[{"source_cache": "artifacts/niacin-precursors-sources/nmrk2016.paragraphs.txt", "locator": "Normalized full-text paragraphs 30–30 (0-based)", "start_char": 33613, "end_char": 35106, "file_sha256": "fcbd5465aff51c9870d65fc9812edbad2cdf2af8bb16b6afb3170d7f0503178a", "text_sha256": "e43865f05c251c7fbb357b31c7968056ae1b58fb1d0f4e61216e5013cb928a41"}, {"source_cache": "artifacts/niacin-precursors-sources/nmrk2016.paragraphs.txt", "locator": "Normalized full-text paragraphs 48–48 (0-based)", "start_char": 46035, "end_char": 46419, "file_sha256": "fcbd5465aff51c9870d65fc9812edbad2cdf2af8bb16b6afb3170d7f0503178a", "text_sha256": "4261a1ca6a50f8b37fd569171c8a9111b9a5ee53b2504811a46cfb40badcb90c"}]

tissue_or_cell_type

NIH/3T3 fibroblasts

Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 409–421

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Murine NRK gain/loss of function in fibroblasts and primary hepatocytes; separate human HepG2 stable-isotope experiments · source_derived_draft · unverified_draft

### b3-pre-mouse-nrk2-nr Transient overexpression of active mouse NRK2 made NIH/3T3 fibroblasts responsive to nicotinamide riboside with increased cellular NAD+; the tested catalytically inactive kinase failed to support the response. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: NR utilization depended on active riboside kinase in this cell model. organism: Mus musculus tissue_or_cell_type: NIH/3T3 fibroblasts experimental_model: Murine NRK gain/loss of function in fibroblasts and primary hepatocytes; separate human HepG2 stable-isotope experiments limitations: Forced expression in mouse fibroblasts; not a human supplementation study. Basal NAD was unchanged by active kinase overexpression without NR. exposure: Transient kinase overexpression with 4 micrograms plasmid; NR 0.5 mM for 6 h under the stated default protocol; mutant comparator NRK1-D36A or NRK2-D35A. evidence_span: {"source_cache": "artifacts/niacin-precursors-sources/nmrk2016.paragraphs.txt", "locator": "Normalized full-text paragraphs 7–7 (0-based)", "start_char": 5559, "end_char": 7104, "file_sha256": "fcbd5465aff51c9870d65fc9812edbad2cdf2af8bb16b6afb3170d7f0503178a", "text_sha256": "ffb453285526cec1670cc565f0b57f3893b48aba7e5014f693f09ea75079348f"} supporting_evidence_spans: [{"source_cache": "artifacts/niacin-precursors-sources/nmrk2016.paragraphs.txt", "locator": "Normalized full-text paragraphs 30–30 (0-based)", "start_char": 33613, "end_char": 35106, "file_sha256": "fcbd5465aff51c9870d65fc9812edbad2cdf2af8bb16b6afb3170d7f0503178a", "text_sha256": "e43865f05c251c7fbb357b31c7968056ae1b58fb1d0f4e61216e5013cb928a41"}, {"source_cache": "artifacts/niacin-precursors-sources/nmrk2016.paragraphs.txt", "locator": "Normalized full-text paragraphs 48–48 (0-based)", "start_char": 46035, "end_char": 46419, "file_sha256": "fcbd5465aff51c9870d65fc9812edbad2cdf2af8bb16b6afb3170d7f0503178a", "text_sha256": "4261a1ca6a50f8b37fd569171c8a9111b9a5ee53b2504811a46cfb40badcb90c"}] [b3-pre-nmrk2016] NRK1 controls nicotinamide mononucleotide and nicotinamide riboside metabolism in mammalian cells. (2016). https://pubmed.ncbi.nlm.nih.gov/27725675/ DOI: 10.1038/ncomms13103

evidence_span

{"source_cache": "artifacts/niacin-precursors-sources/nmnat2002.abstract.txt", "locator": "Indexed primary abstract", "start_char": 0, "end_char": 826, "file_sha256": "5064cc6a7b31875eeaea8def5544c3cce75a971f73aa74f332d89e06c3c54477", "text_sha256": "5064cc6a7b31875eeaea8def5544c3cce75a971f73aa74f332d89e06c3c54477"}

experimental_model

Cloned, expressed and purified recombinant human NMNAT2

exposure

Biochemical or structural assay; no dietary intervention

limitations

Purified-enzyme evidence does not establish dietary intake requirements or clinical outcomes.

nutrient_topic

Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)

organism

Homo sapiens

plain_language

The same human isozyme processes either the amidated or deamidated mononucleotide.

primary_references

[b3-pre-nmnat2002] Identification of a novel human nicotinamide mononucleotide adenylyltransferase. (2002). https://pubmed.ncbi.nlm.nih.gov/12359228/ DOI: 10.1016/s0006-291x(02)02285-4

tissue_or_cell_type

Purified recombinant protein; no intact tissue

Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 302–313

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cloned, expressed and purified recombinant human NMNAT2 · source_derived_draft · unverified_draft

### b3-pre-nmnat2-nmn Purified recombinant human NMNAT2 has adenylyltransferase activity toward NMN, supporting NAD+ formation. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The same human isozyme processes either the amidated or deamidated mononucleotide. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Cloned, expressed and purified recombinant human NMNAT2 limitations: Purified-enzyme evidence does not establish dietary intake requirements or clinical outcomes. exposure: Biochemical or structural assay; no dietary intervention evidence_span: {"source_cache": "artifacts/niacin-precursors-sources/nmnat2002.abstract.txt", "locator": "Indexed primary abstract", "start_char": 0, "end_char": 826, "file_sha256": "5064cc6a7b31875eeaea8def5544c3cce75a971f73aa74f332d89e06c3c54477", "text_sha256": "5064cc6a7b31875eeaea8def5544c3cce75a971f73aa74f332d89e06c3c54477"} [b3-pre-nmnat2002] Identification of a novel human nicotinamide mononucleotide adenylyltransferase. (2002). https://pubmed.ncbi.nlm.nih.gov/12359228/ DOI: 10.1016/s0006-291x(02)02285-4

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/niacin-precursors-sources/nmrk2016.paragraphs.txt", "locator": "Normalized full-text paragraphs 14–14 (0-based)", "start_char": 14813, "end_char": 16096, "file_sha256": "fcbd5465aff51c9870d65fc9812edbad2cdf2af8bb16b6afb3170d7f0503178a", "text_sha256": "fcfc45b2ce45c05afffe5608ea3be48fe50bd17083c12f5b0993f3bc183da63f"}

experimental_model

Murine NRK gain/loss of function in fibroblasts and primary hepatocytes; separate human HepG2 stable-isotope experiments

exposure

0.5 mM NMN for 6 h (Fig. 5e)

limitations

Isolated hepatocytes. Whole-animal liver retained substantial response after injected NR/NMN; the claim is not universal direct-uptake exclusion.

nutrient_topic

Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)

organism

Mus musculus

plain_language

The precursor response required NRK1 in these isolated liver cells.

primary_references

[b3-pre-nmrk2016] NRK1 controls nicotinamide mononucleotide and nicotinamide riboside metabolism in mammalian cells. (2016). https://pubmed.ncbi.nlm.nih.gov/27725675/ DOI: 10.1038/ncomms13103

supporting_evidence_spans

[{"source_cache": "artifacts/niacin-precursors-sources/nmrk2016.paragraphs.txt", "locator": "Normalized full-text paragraphs 52–52 (0-based)", "start_char": 47696, "end_char": 48288, "file_sha256": "fcbd5465aff51c9870d65fc9812edbad2cdf2af8bb16b6afb3170d7f0503178a", "text_sha256": "541856eddb8e5c1162040cb1e010a6d556de92ee36f223d0da751b4c53b06104"}]

tissue_or_cell_type

Primary hepatocytes from male mice aged 10–15 weeks

trigger_kind

machinery_impairment Imported condition classification; unverified.

Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 437–449

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Murine NRK gain/loss of function in fibroblasts and primary hepatocytes; separate human HepG2 stable-isotope experiments · source_derived_draft · unverified_draft

### b3-pre-nrk1ko-nmn Primary hepatocytes from Nmrk1-knockout mice failed to increase NAD+ after NMN treatment, whereas wild-type hepatocytes responded. Condition category: machinery_impairment nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The precursor response required NRK1 in these isolated liver cells. organism: Mus musculus tissue_or_cell_type: Primary hepatocytes from male mice aged 10–15 weeks experimental_model: Murine NRK gain/loss of function in fibroblasts and primary hepatocytes; separate human HepG2 stable-isotope experiments limitations: Isolated hepatocytes. Whole-animal liver retained substantial response after injected NR/NMN; the claim is not universal direct-uptake exclusion. exposure: 0.5 mM NMN for 6 h (Fig. 5e) evidence_span: {"source_cache": "artifacts/niacin-precursors-sources/nmrk2016.paragraphs.txt", "locator": "Normalized full-text paragraphs 14–14 (0-based)", "start_char": 14813, "end_char": 16096, "file_sha256": "fcbd5465aff51c9870d65fc9812edbad2cdf2af8bb16b6afb3170d7f0503178a", "text_sha256": "fcfc45b2ce45c05afffe5608ea3be48fe50bd17083c12f5b0993f3bc183da63f"} supporting_evidence_spans: [{"source_cache": "artifacts/niacin-precursors-sources/nmrk2016.paragraphs.txt", "locator": "Normalized full-text paragraphs 52–52 (0-based)", "start_char": 47696, "end_char": 48288, "file_sha256": "fcbd5465aff51c9870d65fc9812edbad2cdf2af8bb16b6afb3170d7f0503178a", "text_sha256": "541856eddb8e5c1162040cb1e010a6d556de92ee36f223d0da751b4c53b06104"}] [b3-pre-nmrk2016] NRK1 controls nicotinamide mononucleotide and nicotinamide riboside metabolism in mammalian cells. (2016). https://pubmed.ncbi.nlm.nih.gov/27725675/ DOI: 10.1038/ncomms13103

evidence_span

{"source_cache": "artifacts/niacin-redox-sources/slc25a51-2020.author.txt", "locator": "Publisher PDF, results; page/figure identified by adjacent text", "start_char": 18765, "end_char": 19225, "file_sha256": "8348dbfda6d16d576bb64301f0c75f1488e90e33c4a72213b69756bed21d047d", "text_sha256": "121f48fd5cc272acc24a9ca1610c801423a98e3e44f7851e649c8454750e7fb0"}

experimental_model

Isolated mitochondria substrate comparison

exposure

Exogenous NAD+, nicotinamide or NMN

limitations

Does not imply oral NAM/NMN cannot contribute to mitochondrial NAD after extramitochondrial metabolism; this is an isolated-organelle test.

nutrient_topic

Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)

organism

Homo sapiens

plain_language

These precursors were not interchangeable with intact NAD in this uptake experiment.

primary_references

[slc25a51-2020] SLC25A51 is a mammalian mitochondrial NAD+ transporter. (2020). https://pubmed.ncbi.nlm.nih.gov/32906142/ DOI: 10.1038/s41586-020-2741-7

tissue_or_cell_type

Isolated human-cell mitochondria

Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 1068–1079

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Isolated mitochondria substrate comparison · source_derived_draft · unverified_draft

### b3-redox-slc25a51-nam-nmn-null Unlike NAD+, exogenous nicotinamide or NMN did not replenish matrix NAD+ in the isolated-mitochondrial assay. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: These precursors were not interchangeable with intact NAD in this uptake experiment. organism: Homo sapiens tissue_or_cell_type: Isolated human-cell mitochondria experimental_model: Isolated mitochondria substrate comparison limitations: Does not imply oral NAM/NMN cannot contribute to mitochondrial NAD after extramitochondrial metabolism; this is an isolated-organelle test. exposure: Exogenous NAD+, nicotinamide or NMN evidence_span: {"source_cache": "artifacts/niacin-redox-sources/slc25a51-2020.author.txt", "locator": "Publisher PDF, results; page/figure identified by adjacent text", "start_char": 18765, "end_char": 19225, "file_sha256": "8348dbfda6d16d576bb64301f0c75f1488e90e33c4a72213b69756bed21d047d", "text_sha256": "121f48fd5cc272acc24a9ca1610c801423a98e3e44f7851e649c8454750e7fb0"} [slc25a51-2020] SLC25A51 is a mammalian mitochondrial NAD+ transporter. (2020). https://pubmed.ncbi.nlm.nih.gov/32906142/ DOI: 10.1038/s41586-020-2741-7

cell_type

experimental cells

experimental_model

Biochemical and cellular assays

limitations

Recent 2026 finding; no dietary-dose inference.

organism

mammalian

Selenium: literature corrections and mechanism additions · lines 438–448

Metabolic Ledger literature curation, 17 September 2026; primary papers linked individually · supports · Biochemical and cellular assays · secondary_verified · secondary_verified

## selenoo-hydrolyzes-nad SELENOO can split NAD into two smaller molecules. SELENOO catalyzes NAD+ hydrolysis to NMN and AMP. Organism: mammalian Cell type: experimental cells Experimental model: Biochemical and cellular assays Limitations: Recent 2026 finding; no dietary-dose inference. Primary reference: [NAD+ hydrolysis catalyzed by SelO is required for mitochondrial homeostasis](https://pubmed.ncbi.nlm.nih.gov/41806834/)