Norepinephrine

evidence_span

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experimental_model

Human DBH X-ray crystallography

exposure

Crystal structure at 2.9 angstrom resolution

limitations

Open and closed conformations were observed; the proposed catalytic alternation and fully occupied binuclear states require further evidence. Do not equate a structural model with proof of psychiatric effects from copper intake.

nutrient_topic

Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper

organism

Human protein

plain_language

Copper is part of the enzyme that converts one neurotransmitter into another.

primary_references

[copper-p27152332] The crystal structure of human dopamine β-hydroxylase at 2.9 Å resolution. (2016). https://pubmed.ncbi.nlm.nih.gov/27152332/ DOI: 10.1126/sciadv.1500980

tissue_or_cell_type

Purified dimeric enzyme

Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 1079–1090

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human DBH X-ray crystallography · source_derived_draft · unverified_draft

### copper-dbh-neurotransmitter-step Human DBH is the copper-enzyme step converting dopamine to norepinephrine; the study resolved its catalytic-core architecture. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Copper is part of the enzyme that converts one neurotransmitter into another. organism: Human protein tissue_or_cell_type: Purified dimeric enzyme experimental_model: Human DBH X-ray crystallography limitations: Open and closed conformations were observed; the proposed catalytic alternation and fully occupied binuclear states require further evidence. Do not equate a structural model with proof of psychiatric effects from copper intake. exposure: Crystal structure at 2.9 angstrom resolution evidence_span: {"source_cache": "artifacts/copper-research/27152332.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "984a9036d5157e29cdef55d42201887d3ff43cf533185148ba4e3f5c143ced09", "start_char": 0, "end_char": 1325, "text_sha256": "984a9036d5157e29cdef55d42201887d3ff43cf533185148ba4e3f5c143ced09"} [copper-p27152332] The crystal structure of human dopamine β-hydroxylase at 2.9 Å resolution. (2016). https://pubmed.ncbi.nlm.nih.gov/27152332/ DOI: 10.1126/sciadv.1500980

cross_nutrient

Vitamin C chemistry in collagen, modified-lysine/carnitine metabolism or copper-dependent peptide/catecholamine processing.

experimental_model

Human SH-SY5Y neuroblastoma cultures

exposure

100 micromolar ascorbate added to human SH-SY5Y culture; time course through six hours and longer; Fig.1.

limitations

Figure 1 measures cellular content; it is not a purified DBH flux assay or demonstration of symptom improvement in people.

nutrient_topic

Vitamin C research collection; topical membership is not evidence of a direct dietary effect. · Vitamin C

organism

Homo sapiens

plain_language

Vitamin C increased the neurotransmitter pool in these cultured neuronal cells.

primary_references

[may2012] Mechanisms of ascorbic acid stimulation of norepinephrine synthesis in neuronal cells. (2012). https://pubmed.ncbi.nlm.nih.gov/22925890/ DOI: 10.1016/j.bbrc.2012.08.054

tissue_or_cell_type

Neuronal tumor cell line

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 820–831

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human SH-SY5Y neuroblastoma cultures · source_derived_draft · unverified_draft

### vc-enzyme-neuronal-ne-accumulation Adding 100 micromolar ascorbate to SH-SY5Y cultures increased intracellular norepinephrine over six hours in parallel with ascorbate accumulation. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin C increased the neurotransmitter pool in these cultured neuronal cells. organism: Homo sapiens tissue_or_cell_type: Neuronal tumor cell line experimental_model: Human SH-SY5Y neuroblastoma cultures limitations: Figure 1 measures cellular content; it is not a purified DBH flux assay or demonstration of symptom improvement in people. cross_nutrient: Vitamin C chemistry in collagen, modified-lysine/carnitine metabolism or copper-dependent peptide/catecholamine processing. exposure: 100 micromolar ascorbate added to human SH-SY5Y culture; time course through six hours and longer; Fig.1. [may2012] Mechanisms of ascorbic acid stimulation of norepinephrine synthesis in neuronal cells. (2012). https://pubmed.ncbi.nlm.nih.gov/22925890/ DOI: 10.1016/j.bbrc.2012.08.054

cross_nutrient

Ascorbate interacts with the pterin cofactor pathway supporting amino-acid-derived catecholamine synthesis; sepiapterin is kept distinct from BH4.

experimental_model

Human SH-SY5Y neuroblastoma cultures

exposure

Sepiapterin dose series with or without 50 micromolar ascorbate, 24 hours; Fig.3C.

limitations

Fig.3C tests sepiapterin, not direct BH4 dosing; BH4 recycling by ascorbate is an interpretation rather than a measured reaction in this experiment.

nutrient_topic

Vitamin C research collection; topical membership is not evidence of a direct dietary effect. · Vitamin C

organism

Homo sapiens

plain_language

Supporting a second cofactor pathway enhanced the neuronal response to vitamin C.

primary_references

[may2012] Mechanisms of ascorbic acid stimulation of norepinephrine synthesis in neuronal cells. (2012). https://pubmed.ncbi.nlm.nih.gov/22925890/ DOI: 10.1016/j.bbrc.2012.08.054

tissue_or_cell_type

Neuronal tumor cell line

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 846–857

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human SH-SY5Y neuroblastoma cultures · source_derived_draft · unverified_draft

### vc-enzyme-sepiapterin-co-response Sepiapterin increased norepinephrine content in SH-SY5Y cultures and 50 micromolar ascorbate increased the response further after 24 hours. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Supporting a second cofactor pathway enhanced the neuronal response to vitamin C. organism: Homo sapiens tissue_or_cell_type: Neuronal tumor cell line experimental_model: Human SH-SY5Y neuroblastoma cultures limitations: Fig.3C tests sepiapterin, not direct BH4 dosing; BH4 recycling by ascorbate is an interpretation rather than a measured reaction in this experiment. cross_nutrient: Ascorbate interacts with the pterin cofactor pathway supporting amino-acid-derived catecholamine synthesis; sepiapterin is kept distinct from BH4. exposure: Sepiapterin dose series with or without 50 micromolar ascorbate, 24 hours; Fig.3C. [may2012] Mechanisms of ascorbic acid stimulation of norepinephrine synthesis in neuronal cells. (2012). https://pubmed.ncbi.nlm.nih.gov/22925890/ DOI: 10.1016/j.bbrc.2012.08.054

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Reported treatment responses in a small genetic case series.

limitations

This is a specific drug bypass, not evidence that tyrosine or ascorbate supplements correct the defect.

nutrient_topic

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

plain_language

A downstream precursor can bypass a particular broken step.

primary_references

Mutations in CYB561 Causing a Novel Orthostatic Hypotension Syndrome. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29343526/ · DOI 10.1161/CIRCRESAHA.117.311949

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism 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 · Reported treatment responses in a small genetic case series. · source_derived_draft · unverified_draft

## l-tyrosine-cyb-bypass A downstream precursor can bypass a particular broken step. The CYB561-deficient patients responded favorably to L-dihydroxyphenylserine, a precursor that can be converted directly to norepinephrine. Model: Reported treatment responses in a small genetic case series. Limitations: This is a specific drug bypass, not evidence that tyrosine or ascorbate supplements correct the defect. Evidence access: Primary abstract Mutations in CYB561 Causing a Novel Orthostatic Hypotension Syndrome. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29343526/ · DOI 10.1161/CIRCRESAHA.117.311949

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Two human families; genetic analysis with supporting Cyb561 knockout mouse results.

limitations

The human defect and mouse corroboration are distinct evidence; ordinary dietary vitamin C deficiency was not the intervention.

nutrient_topic

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

plain_language

A normal blood enzyme test can miss a cofactor problem inside a vesicle.

primary_references

Mutations in CYB561 Causing a Novel Orthostatic Hypotension Syndrome. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29343526/ · DOI 10.1161/CIRCRESAHA.117.311949

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism 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 · Two human families; genetic analysis with supporting Cyb561 knockout mouse results. · source_derived_draft · unverified_draft

## l-tyrosine-cyb-vesicle A normal blood enzyme test can miss a cofactor problem inside a vesicle. Pathogenic CYB561 variants in four patients accompanied very low norepinephrine and epinephrine despite normal plasma DBH activity; impaired intravesicular ascorbate support was the proposed functional block. Model: Two human families; genetic analysis with supporting Cyb561 knockout mouse results. Limitations: The human defect and mouse corroboration are distinct evidence; ordinary dietary vitamin C deficiency was not the intervention. Evidence access: Primary abstract Mutations in CYB561 Causing a Novel Orthostatic Hypotension Syndrome. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29343526/ · DOI 10.1161/CIRCRESAHA.117.311949

evidence_access

Primary abstract

experimental_model

Human enzyme transition-state and inhibitor kinetics; structural analysis.

limitations

Shared SAM use does not prove that tyrosine supplementation drains folate, B12 or methionine.

nutrient_topic

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

plain_language

A downstream branch uses a methyl donor from methionine metabolism.

primary_references

Transition-State Analogues of Phenylethanolamine N-Methyltransferase. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32702980/ · DOI 10.1021/jacs.0c05446

L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 44–50

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human enzyme transition-state and inhibitor kinetics; structural analysis. · source_derived_draft · unverified_draft

## l-tyrosine-pnmt-methyl A downstream branch uses a methyl donor from methionine metabolism. Human PNMT transfers a methyl group from SAM to norepinephrine during epinephrine synthesis. Model: Human enzyme transition-state and inhibitor kinetics; structural analysis. Limitations: Shared SAM use does not prove that tyrosine supplementation drains folate, B12 or methionine. Evidence access: Primary abstract Transition-State Analogues of Phenylethanolamine N-Methyltransferase. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32702980/ · DOI 10.1021/jacs.0c05446

evidence_span

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experimental_model

Immortalized mouse brown adipocyte cell lines with selective beta-adrenergic agonists and antagonists

exposure

Norepinephrine, the beta-3 selective agonist CL316,243, and subtype-selective antagonists

limitations

A cell-line dissection of receptor subtypes. The additive cAMP response indicates the subtypes are not redundant, but these are immortalized cells.

nutrient_topic

Cold water immersion research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Cold water immersion

organism

Mouse cell lines

plain_language

Three different receptors for the same messenger all feed the heat gene, and together they do more than any one alone.

primary_references

[cold-p7738011] Regulation of the uncoupling protein gene (Ucp) by beta 1, beta 2, and beta 3-adrenergic receptor subtypes in immortalized brown adipose cell lines. (1995). https://pubmed.ncbi.nlm.nih.gov/7738011/ DOI: 10.1074/jbc.270.18.10723

tissue_or_cell_type

Brown adipocytes

Cold water immersion: cold sensing, heat production, the catecholamine axis and what repeated exposure changes (2026-09-19) · lines 364–375

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Immortalized mouse brown adipocyte cell lines with selective beta-adrenergic agonists and antagonists · source_derived_draft · unverified_draft

### cold-beta-receptors-ucp1 UCP1 expression could be induced by any of the beta-1, beta-2 or beta-3 adrenergic receptor subtypes, but the greatest response came from stimulating all three simultaneously, and beta-3 stimulation did not prevent norepinephrine from further raising adenylyl cyclase activity, suggesting an additive cAMP response. Condition category: normal nutrient_topic: Cold water immersion research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Three different receptors for the same messenger all feed the heat gene, and together they do more than any one alone. organism: Mouse cell lines tissue_or_cell_type: Brown adipocytes experimental_model: Immortalized mouse brown adipocyte cell lines with selective beta-adrenergic agonists and antagonists limitations: A cell-line dissection of receptor subtypes. The additive cAMP response indicates the subtypes are not redundant, but these are immortalized cells. exposure: Norepinephrine, the beta-3 selective agonist CL316,243, and subtype-selective antagonists evidence_span: {"source_cache": "artifacts/cold-research/7738011.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b1c5506f21f40d6674727a5fc3344f2b02f7fc9f2f1e911fd04bfecfc2399175", "start_char": 0, "end_char": 2592, "text_sha256": "b1c5506f21f40d6674727a5fc3344f2b02f7fc9f2f1e911fd04bfecfc2399175"} [cold-p7738011] Regulation of the uncoupling protein gene (Ucp) by beta 1, beta 2, and beta 3-adrenergic receptor subtypes in immortalized brown adipose cell lines. (1995). https://pubmed.ncbi.nlm.nih.gov/7738011/ DOI: 10.1074/jbc.270.18.10723

evidence_span

{"source_cache": "artifacts/cold-research/6323422.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dac85ce0ad7c7d5994b97d55b129050a0e7ca8bf96943578d272054db6a07a62", "start_char": 0, "end_char": 1346, "text_sha256": "dac85ce0ad7c7d5994b97d55b129050a0e7ca8bf96943578d272054db6a07a62"}

experimental_model

Copper titration of bovine adrenal dopamine beta-hydroxylase followed by NMR, EPR and inhibitor kinetics

exposure

Titration with copper and measurement of catalytic rate

limitations

Stoichiometry measured three independent ways. It establishes how much copper the enzyme needs, not how much copper a person needs.

nutrient_topic

Cold water immersion research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Cold water immersion

organism

Bovine enzyme

plain_language

The enzyme that turns dopamine into noradrenaline needs exactly eight copper atoms to work fully.

primary_references

[cold-p6323422] Kinetic and spectroscopic studies of the interaction of copper with dopamine beta-hydroxylase. (1984). https://pubmed.ncbi.nlm.nih.gov/6323422/ DOI: 10.1016/s0021-9258(17)43105-x

tissue_or_cell_type

Adrenal medulla enzyme

Cold water immersion: cold sensing, heat production, the catecholamine axis and what repeated exposure changes (2026-09-19) · lines 559–570

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Copper titration of bovine adrenal dopamine beta-hydroxylase followed by NMR, EPR and inhibitor kinetics · source_derived_draft · unverified_draft

### cold-dbh-copper-stoichiometry Dopamine beta-hydroxylase specifically binds 8 moles of copper per mole of tetramer, confirmed by radiolabel, atomic absorption, NMR and EPR titration, and catalytic rate increased with copper up to that ratio and was constant thereafter, so this stoichiometry is required for maximal activity. Condition category: normal nutrient_topic: Cold water immersion research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: The enzyme that turns dopamine into noradrenaline needs exactly eight copper atoms to work fully. organism: Bovine enzyme tissue_or_cell_type: Adrenal medulla enzyme experimental_model: Copper titration of bovine adrenal dopamine beta-hydroxylase followed by NMR, EPR and inhibitor kinetics limitations: Stoichiometry measured three independent ways. It establishes how much copper the enzyme needs, not how much copper a person needs. exposure: Titration with copper and measurement of catalytic rate evidence_span: {"source_cache": "artifacts/cold-research/6323422.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dac85ce0ad7c7d5994b97d55b129050a0e7ca8bf96943578d272054db6a07a62", "start_char": 0, "end_char": 1346, "text_sha256": "dac85ce0ad7c7d5994b97d55b129050a0e7ca8bf96943578d272054db6a07a62"} [cold-p6323422] Kinetic and spectroscopic studies of the interaction of copper with dopamine beta-hydroxylase. (1984). https://pubmed.ncbi.nlm.nih.gov/6323422/ DOI: 10.1016/s0021-9258(17)43105-x

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/cold-research/19187776.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "007fc44fbc02ff64861f816e90139d469f59bbe7d95bd22c6e4daecd38070b30", "start_char": 0, "end_char": 1051, "text_sha256": "007fc44fbc02ff64861f816e90139d469f59bbe7d95bd22c6e4daecd38070b30"}

experimental_model

UCP1-ablated C57Bl6 mice housed at thermoneutrality on control or high-fat diet

exposure

Thermoneutral housing with control and high-fat diets

limitations

Housing temperature is the whole point: the obesogenic effect appears only when thermal stress is removed. Earlier studies missed it for that reason.

nutrient_topic

Cold water immersion research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Cold water immersion

organism

Mouse

plain_language

Remove the heat protein and take away the cold, and the animal gets fat.

primary_references

[cold-p19187776] UCP1 ablation induces obesity and abolishes diet-induced thermogenesis in mice exempt from thermal stress by living at thermoneutrality. (2009). https://pubmed.ncbi.nlm.nih.gov/19187776/ DOI: 10.1016/j.cmet.2008.12.014

tissue_or_cell_type

Brown adipose tissue and whole body

trigger_kind

machinery_impairment Imported condition classification; unverified.

Cold water immersion: cold sensing, heat production, the catecholamine axis and what repeated exposure changes (2026-09-19) · lines 325–336

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · UCP1-ablated C57Bl6 mice housed at thermoneutrality on control or high-fat diet · source_derived_draft · unverified_draft

### cold-ucp1-ablation-obesity At thermoneutrality, UCP1 ablation induced obesity even on control diet and vastly augmented diet-induced obesity, and high-fat diet increased norepinephrine-induced thermogenesis in wild-type but not UCP1-ablated mice, showing diet-induced thermogenesis fully emanates from UCP1 activity. Condition category: machinery_impairment nutrient_topic: Cold water immersion research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Remove the heat protein and take away the cold, and the animal gets fat. organism: Mouse tissue_or_cell_type: Brown adipose tissue and whole body experimental_model: UCP1-ablated C57Bl6 mice housed at thermoneutrality on control or high-fat diet limitations: Housing temperature is the whole point: the obesogenic effect appears only when thermal stress is removed. Earlier studies missed it for that reason. exposure: Thermoneutral housing with control and high-fat diets evidence_span: {"source_cache": "artifacts/cold-research/19187776.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "007fc44fbc02ff64861f816e90139d469f59bbe7d95bd22c6e4daecd38070b30", "start_char": 0, "end_char": 1051, "text_sha256": "007fc44fbc02ff64861f816e90139d469f59bbe7d95bd22c6e4daecd38070b30"} [cold-p19187776] UCP1 ablation induces obesity and abolishes diet-induced thermogenesis in mice exempt from thermal stress by living at thermoneutrality. (2009). https://pubmed.ncbi.nlm.nih.gov/19187776/ DOI: 10.1016/j.cmet.2008.12.014

experimental_model

Ten-day randomized trial; 3 g/day of each amino acid, followed by public-speaking stress

limitations

Small combination trial; authors' proposed normalization is an interpretation, not a proven lysine-specific mechanism.

organism

Homo sapiens

plain_language

The mixture did not simply suppress all stress hormones.

primary_references

[jezova2005] Subchronic treatment with amino acid mixture of L-lysine and L-arginine modifies neuroendocrine activation during psychosocial stress in subjects with high trait anxiety (2005). https://pubmed.ncbi.nlm.nih.gov/16117182/ DOI: 10.1080/10284150500162937

tissue_or_cell_type

Blood stress hormones and cardiovascular measurements

L-Lysine: mechanism-first literature curation (2026-09-17) · lines 739–747

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ten-day randomized trial; 3 g/day of each amino acid, followed by public-speaking stress · source_derived_draft · unverified_draft

### lysine-arginine-stress-hormones In 29 high-trait-anxiety participants, lysine plus arginine increased stress-evoked ACTH, cortisol, adrenaline, and noradrenaline responses without changing heart-rate or blood-pressure responses. Plain language: The mixture did not simply suppress all stress hormones. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Blood stress hormones and cardiovascular measurements experimental_model: Ten-day randomized trial; 3 g/day of each amino acid, followed by public-speaking stress limitations: Small combination trial; authors' proposed normalization is an interpretation, not a proven lysine-specific mechanism. [jezova2005] Subchronic treatment with amino acid mixture of L-lysine and L-arginine modifies neuroendocrine activation during psychosocial stress in subjects with high trait anxiety (2005). https://pubmed.ncbi.nlm.nih.gov/16117182/ DOI: 10.1080/10284150500162937

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Clinical boundary for the copper/ascorbate-dependent dopamine beta-hydroxylase pathway.

experimental_model

Five volunteers studied after three months of vitamin C deprivation and again after four months of repletion.

exposure

Clinical scurvy; forearm blood flow, pressure, catecholamines and responses to lower-body negative pressure, norepinephrine and tyramine.

limitations

Plasma catecholamines do not measure all neuronal stores or DBH flux; limited power in five participants.

nutrient_topic

Vitamin C research collection; topical membership is not evidence of a direct dietary effect. · Vitamin C

organism

Homo sapiens

plain_language

An enzyme’s vitamin C requirement did not translate into complete failure of the human stress-signal system.

primary_references

[c-abboud1970] Autonomic reflexes and vascular reactivity in experimental scurvy in man (1970). https://pubmed.ncbi.nlm.nih.gov/5411783/ DOI: 10.1172/jci106239

tissue_or_cell_type

Human blood or whole-person endpoints

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1541–1552

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Five volunteers studied after three months of vitamin C deprivation and again after four months of repletion. · source_derived_draft · unverified_draft

### c-scurvy-catecholamine-reflex-boundary Resting plasma catecholamines and hemodynamic measurements did not change significantly after correction; reflex tachycardia and bradycardia were similar in the deficient and repleted studies. Condition category: nutrient_deficiency nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: An enzyme’s vitamin C requirement did not translate into complete failure of the human stress-signal system. organism: Homo sapiens tissue_or_cell_type: Human blood or whole-person endpoints experimental_model: Five volunteers studied after three months of vitamin C deprivation and again after four months of repletion. limitations: Plasma catecholamines do not measure all neuronal stores or DBH flux; limited power in five participants. exposure: Clinical scurvy; forearm blood flow, pressure, catecholamines and responses to lower-body negative pressure, norepinephrine and tyramine. cross_nutrient: Clinical boundary for the copper/ascorbate-dependent dopamine beta-hydroxylase pathway. [c-abboud1970] Autonomic reflexes and vascular reactivity in experimental scurvy in man (1970). https://pubmed.ncbi.nlm.nih.gov/5411783/ DOI: 10.1172/jci106239

availability_state

nutrient_deficiency Imported condition classification; unverified.

experimental_model

Five volunteers studied after three months of vitamin C deprivation and again after four months of repletion.

exposure

Clinical scurvy; forearm blood flow, pressure, catecholamines and responses to lower-body negative pressure, norepinephrine and tyramine.

limitations

Does not isolate endothelial, smooth-muscle or collagen mechanisms.

nutrient_topic

Vitamin C research collection; topical membership is not evidence of a direct dietary effect. · Vitamin C

organism

Homo sapiens

plain_language

The blood vessels responded less strongly to some constricting signals during shortage.

primary_references

[c-abboud1970] Autonomic reflexes and vascular reactivity in experimental scurvy in man (1970). https://pubmed.ncbi.nlm.nih.gov/5411783/ DOI: 10.1172/jci106239

tissue_or_cell_type

Human blood or whole-person endpoints

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1529–1539

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Five volunteers studied after three months of vitamin C deprivation and again after four months of repletion. · source_derived_draft · unverified_draft

### c-scurvy-vascular-responsiveness Forearm vasoconstriction to intra-arterial norepinephrine and tyramine was greater after repletion; four subjects also had lower resistance-vessel responsiveness to lower-body negative pressure during deficiency. Condition category: nutrient_deficiency nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: The blood vessels responded less strongly to some constricting signals during shortage. organism: Homo sapiens tissue_or_cell_type: Human blood or whole-person endpoints experimental_model: Five volunteers studied after three months of vitamin C deprivation and again after four months of repletion. limitations: Does not isolate endothelial, smooth-muscle or collagen mechanisms. exposure: Clinical scurvy; forearm blood flow, pressure, catecholamines and responses to lower-body negative pressure, norepinephrine and tyramine. [c-abboud1970] Autonomic reflexes and vascular reactivity in experimental scurvy in man (1970). https://pubmed.ncbi.nlm.nih.gov/5411783/ DOI: 10.1172/jci106239