Scurvy

Nutritional MONDO:0009412 Pathograph 8 Vitamin Deficiency Disease

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2
Pathophys.
7
Phenotypes
8
Pathograph
1
Treatments
10
References
2
Deep Research
⚙

Pathophysiology

2
Collagen Synthesis Impairment
Vitamin C (ascorbic acid) is essential for hydroxylation of proline and lysine residues in collagen synthesis by prolyl and lysyl hydroxylases. Deficiency leads to inadequate hydroxyproline and hydroxylysine formation, preventing triple-helix stability and mature cross-links, resulting in defective collagen formation that affects connective tissues throughout the body.
Downstream
Impaired Wound Healing Defective collagen formation impairs tissue repair and wound healing processes.
Gingival Bleeding Impaired collagen in gingival tissues leads to mucosal fragility and bleeding.
Arthralgias Defective collagen in joints and periarticular tissues causes pain and hemarthrosis.
Show evidence (1 reference)
PMID:37366866 SUPPORT
"It leads to a varied presentation, affecting multiple organ systems due to its role in the biochemical reactions of connective tissue synthesis."
This abstract confirms scurvy affects multiple organ systems through its role in connective tissue synthesis, supporting the collagen synthesis impairment mechanism.
Vascular Integrity Failure
Defective collagen in blood vessel walls and basement membranes leads to capillary fragility and increased vascular permeability. This manifests as spontaneous bleeding including petechiae, ecchymoses, and mucosal hemorrhages despite normal coagulation.
Downstream
Perifollicular Hemorrhages Capillary fragility around hair follicles results in characteristic perifollicular bleeding.
Ecchymoses Vascular fragility leads to easy bruising and larger areas of subcutaneous bleeding.
Skin Discoloration Hemorrhage and hemosiderin deposition cause skin pigmentation changes.
Show evidence (1 reference)
PMID:37366866 SUPPORT
"Common manifestations include gingival bleeding, arthralgias, skin discoloration, impaired wound healing, perifollicular hemorrhage, and ecchymoses."
The manifestations of gingival bleeding, perifollicular hemorrhage, and ecchymoses are direct consequences of vascular fragility from defective collagen.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Scurvy Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
●

Phenotypes

7
Blood 3
Perifollicular Hemorrhages FREQUENT Petechiae (HP:0000967)
Show evidence (1 reference)
PMID:37366866 SUPPORT
"Common manifestations include gingival bleeding, arthralgias, skin discoloration, impaired wound healing, perifollicular hemorrhage, and ecchymoses."
Perifollicular hemorrhage is explicitly listed as a common manifestation of scurvy.
Ecchymoses FREQUENT Bruising susceptibility (HP:0000978)
Show evidence (2 references)
PMID:37366866 SUPPORT
"Common manifestations include gingival bleeding, arthralgias, skin discoloration, impaired wound healing, perifollicular hemorrhage, and ecchymoses."
Ecchymoses are explicitly listed as a common manifestation of scurvy.
PMID:37915623 SUPPORT
"He was diagnosed with scurvy due to a long history of staying indoors and inadequate intake of fruits or vegetables."
The case report describes a patient presenting with ecchymoses of both lower extremities, demonstrating this as a key clinical feature.
Gingival Bleeding FREQUENT Gingival bleeding (HP:0000225)
Show evidence (1 reference)
PMID:37366866 SUPPORT
"Common manifestations include gingival bleeding, arthralgias, skin discoloration, impaired wound healing, perifollicular hemorrhage, and ecchymoses."
Gingival bleeding is explicitly listed as a common manifestation.
Integument 1
Impaired Wound Healing FREQUENT Poor wound healing (HP:0001058)
Show evidence (1 reference)
PMID:37366866 SUPPORT
"Common manifestations include gingival bleeding, arthralgias, skin discoloration, impaired wound healing, perifollicular hemorrhage, and ecchymoses."
Impaired wound healing is explicitly listed as a common manifestation.
Constitutional 2
Arthralgias FREQUENT Arthralgia (HP:0002829)
Show evidence (2 references)
PMID:37366866 SUPPORT
"Common manifestations include gingival bleeding, arthralgias, skin discoloration, impaired wound healing, perifollicular hemorrhage, and ecchymoses."
Arthralgias are explicitly listed as a common manifestation.
PMID:37915623 SUPPORT
"Here, we report on a 25-year-old male patient without any underlying conditions who presented with severe pain and ecchymoses of both lower extremities."
The case demonstrates severe pain in the lower extremities as a presenting feature of scurvy.
Fatigue VERY_FREQUENT Fatigue (HP:0012378)
Show evidence (1 reference)
PMID:37915623 SUPPORT
"Scurvy, resulting from vitamin C deficiency, has nonspecific constitutional symptoms, including weakness, malaise, and fatigue."
Weakness, malaise, and fatigue are described as nonspecific constitutional symptoms of scurvy.
Other 1
Skin Discoloration FREQUENT
Show evidence (1 reference)
PMID:37366866 SUPPORT
"Common manifestations include gingival bleeding, arthralgias, skin discoloration, impaired wound healing, perifollicular hemorrhage, and ecchymoses."
Skin discoloration is listed as a common clinical manifestation.
💊

Treatments

1
Vitamin C Supplementation
Action: vitamin C supplementation MAXO:0000109
Oral vitamin C supplementation (100-300 mg daily) rapidly reverses symptoms. Clinical improvement typically begins within 24-48 hours. The condition can be adequately treated and prevented via vitamin C supplementation.
Show evidence (1 reference)
PMID:37366866 SUPPORT
"It can be adequately treated and prevented via vitamin C supplementation."
This confirms that vitamin C supplementation is the adequate treatment and prevention for scurvy.
🌍

Environmental Factors

1
Vitamin C Deficiency
Inadequate dietary intake of vitamin C (ascorbic acid), typically less than 10 mg/day for several weeks to months. Vitamin C is found in citrus fruits, berries, and green vegetables. Inadequate intake may result from poor dietary habits, low socio-economic status, restricted diets, or limited access to fresh fruits and vegetables.
Show evidence (2 references)
PMID:37915623 SUPPORT
"He was diagnosed with scurvy due to a long history of staying indoors and inadequate intake of fruits or vegetables."
This case demonstrates that inadequate intake of fruits and vegetables can lead to scurvy.
PMID:37366866 SUPPORT
"In developed countries, it is mainly diagnosed in the elderly and malnourished individuals and is associated with alcoholism, low socio-economic status, and poor dietary habits."
This confirms that scurvy is associated with poor dietary habits and low socio-economic status leading to inadequate vitamin C intake.
{ }

Source YAML

click to show 
name: Scurvy
creation_date: '2026-01-08T21:52:49Z'
updated_date: '2026-02-17T21:53:14Z'
category: Nutritional
disease_term:
  preferred_term: scurvy
  term:
    id: MONDO:0009412
    label: scurvy
parents:
- Vitamin Deficiency Disease
pathophysiology:
- name: Collagen Synthesis Impairment
  description: >
    Vitamin C (ascorbic acid) is essential for hydroxylation of proline and lysine
    residues in collagen synthesis by prolyl and lysyl hydroxylases. Deficiency leads
    to inadequate hydroxyproline and hydroxylysine formation, preventing triple-helix
    stability and mature cross-links, resulting in defective collagen formation that
    affects connective tissues throughout the body.
  downstream:
  - target: Impaired Wound Healing
    description: Defective collagen formation impairs tissue repair and wound
      healing processes.
  - target: Gingival Bleeding
    description: Impaired collagen in gingival tissues leads to mucosal
      fragility and bleeding.
  - target: Arthralgias
    description: Defective collagen in joints and periarticular tissues causes
      pain and hemarthrosis.
  evidence:
  - reference: PMID:37366866
    reference_title: "Scurvy: Rediscovering a Forgotten Disease."
    supports: SUPPORT
    snippet: "It leads to a varied presentation, affecting multiple organ systems
      due to its role in the biochemical reactions of connective tissue synthesis."
    explanation: "This abstract confirms scurvy affects multiple organ systems through
      its role in connective tissue synthesis, supporting the collagen synthesis impairment
      mechanism."
- name: Vascular Integrity Failure
  description: >
    Defective collagen in blood vessel walls and basement membranes leads to capillary
    fragility and increased vascular permeability. This manifests as spontaneous bleeding
    including petechiae, ecchymoses, and mucosal hemorrhages despite normal coagulation.
  downstream:
  - target: Perifollicular Hemorrhages
    description: Capillary fragility around hair follicles results in
      characteristic perifollicular bleeding.
  - target: Ecchymoses
    description: Vascular fragility leads to easy bruising and larger areas of
      subcutaneous bleeding.
  - target: Skin Discoloration
    description: Hemorrhage and hemosiderin deposition cause skin pigmentation
      changes.
  evidence:
  - reference: PMID:37366866
    reference_title: "Scurvy: Rediscovering a Forgotten Disease."
    supports: SUPPORT
    snippet: "Common manifestations include gingival bleeding, arthralgias, skin discoloration,
      impaired wound healing, perifollicular hemorrhage, and ecchymoses."
    explanation: "The manifestations of gingival bleeding, perifollicular hemorrhage,
      and ecchymoses are direct consequences of vascular fragility from defective
      collagen."
phenotypes:
- category: Dermatological
  name: Perifollicular Hemorrhages
  frequency: FREQUENT
  description: Small hemorrhages around hair follicles due to fragile blood
    vessels from defective collagen.
  phenotype_term:
    preferred_term: perifollicular hemorrhage
    term:
      id: HP:0000967
      label: Petechiae
  evidence:
  - reference: PMID:37366866
    reference_title: "Scurvy: Rediscovering a Forgotten Disease."
    supports: SUPPORT
    snippet: "Common manifestations include gingival bleeding, arthralgias, skin discoloration,
      impaired wound healing, perifollicular hemorrhage, and ecchymoses."
    explanation: "Perifollicular hemorrhage is explicitly listed as a common manifestation
      of scurvy."
- category: Dermatological
  name: Ecchymoses
  frequency: FREQUENT
  description: Larger areas of subcutaneous bleeding appearing as bruises,
    resulting from capillary fragility and impaired collagen formation.
  phenotype_term:
    preferred_term: ecchymoses
    term:
      id: HP:0000978
      label: Bruising susceptibility
  evidence:
  - reference: PMID:37366866
    reference_title: "Scurvy: Rediscovering a Forgotten Disease."
    supports: SUPPORT
    snippet: "Common manifestations include gingival bleeding, arthralgias, skin discoloration,
      impaired wound healing, perifollicular hemorrhage, and ecchymoses."
    explanation: "Ecchymoses are explicitly listed as a common manifestation of scurvy."
  - reference: PMID:37915623
    reference_title: "Scurvy in a young man: a rare case report."
    supports: SUPPORT
    snippet: "He was diagnosed with scurvy due to a long history of staying indoors
      and inadequate intake of fruits or vegetables."
    explanation: "The case report describes a patient presenting with ecchymoses of
      both lower extremities, demonstrating this as a key clinical feature."
- category: Dermatological
  name: Skin Discoloration
  frequency: FREQUENT
  description: Abnormal skin pigmentation and color changes associated with
    hemorrhage and poor wound healing.
  evidence:
  - reference: PMID:37366866
    reference_title: "Scurvy: Rediscovering a Forgotten Disease."
    supports: SUPPORT
    snippet: "Common manifestations include gingival bleeding, arthralgias, skin discoloration,
      impaired wound healing, perifollicular hemorrhage, and ecchymoses."
    explanation: "Skin discoloration is listed as a common clinical manifestation."
- category: Oral
  name: Gingival Bleeding
  frequency: FREQUENT
  description: Spontaneous bleeding and swelling of the gums due to fragile
    mucosa and impaired collagen.
  phenotype_term:
    preferred_term: gingival bleeding
    term:
      id: HP:0000225
      label: Gingival bleeding
  evidence:
  - reference: PMID:37366866
    reference_title: "Scurvy: Rediscovering a Forgotten Disease."
    supports: SUPPORT
    snippet: "Common manifestations include gingival bleeding, arthralgias, skin discoloration,
      impaired wound healing, perifollicular hemorrhage, and ecchymoses."
    explanation: "Gingival bleeding is explicitly listed as a common manifestation."
- category: Musculoskeletal
  name: Arthralgias
  frequency: FREQUENT
  description: Joint pain resulting from hemarthrosis and periarticular
    hemorrhages due to capillary fragility.
  phenotype_term:
    preferred_term: arthralgia
    term:
      id: HP:0002829
      label: Arthralgia
  evidence:
  - reference: PMID:37366866
    reference_title: "Scurvy: Rediscovering a Forgotten Disease."
    supports: SUPPORT
    snippet: "Common manifestations include gingival bleeding, arthralgias, skin discoloration,
      impaired wound healing, perifollicular hemorrhage, and ecchymoses."
    explanation: "Arthralgias are explicitly listed as a common manifestation."
  - reference: PMID:37915623
    reference_title: "Scurvy in a young man: a rare case report."
    supports: SUPPORT
    snippet: "Here, we report on a 25-year-old male patient without any underlying
      conditions who presented with severe pain and ecchymoses of both lower extremities."
    explanation: "The case demonstrates severe pain in the lower extremities as a
      presenting feature of scurvy."
- category: Constitutional
  name: Fatigue
  frequency: VERY_FREQUENT
  description: General weakness and malaise, potentially related to impaired
    carnitine biosynthesis and reduced catecholamine synthesis.
  phenotype_term:
    preferred_term: fatigue
    term:
      id: HP:0012378
      label: Fatigue
  evidence:
  - reference: PMID:37915623
    reference_title: "Scurvy in a young man: a rare case report."
    supports: SUPPORT
    snippet: "Scurvy, resulting from vitamin C deficiency, has nonspecific constitutional
      symptoms, including weakness, malaise, and fatigue."
    explanation: "Weakness, malaise, and fatigue are described as nonspecific constitutional
      symptoms of scurvy."
- category: Dermatological
  name: Impaired Wound Healing
  frequency: FREQUENT
  description: Delayed or abnormal wound healing due to defective collagen
    synthesis and impaired tissue repair.
  phenotype_term:
    preferred_term: impaired wound healing
    term:
      id: HP:0001058
      label: Poor wound healing
  evidence:
  - reference: PMID:37366866
    reference_title: "Scurvy: Rediscovering a Forgotten Disease."
    supports: SUPPORT
    snippet: "Common manifestations include gingival bleeding, arthralgias, skin discoloration,
      impaired wound healing, perifollicular hemorrhage, and ecchymoses."
    explanation: "Impaired wound healing is explicitly listed as a common manifestation."
environmental:
- name: Vitamin C Deficiency
  description: >
    Inadequate dietary intake of vitamin C (ascorbic acid), typically less than 10
    mg/day
    for several weeks to months. Vitamin C is found in citrus fruits, berries, and
    green vegetables. Inadequate intake may result from poor dietary habits, low
    socio-economic status, restricted diets, or limited access to fresh fruits and
    vegetables.
  evidence:
  - reference: PMID:37915623
    reference_title: "Scurvy in a young man: a rare case report."
    supports: SUPPORT
    snippet: "He was diagnosed with scurvy due to a long history of staying indoors
      and inadequate intake of fruits or vegetables."
    explanation: "This case demonstrates that inadequate intake of fruits and vegetables
      can lead to scurvy."
  - reference: PMID:37366866
    reference_title: "Scurvy: Rediscovering a Forgotten Disease."
    supports: SUPPORT
    snippet: "In developed countries, it is mainly diagnosed in the elderly and malnourished
      individuals and is associated with alcoholism, low socio-economic status, and
      poor dietary habits."
    explanation: "This confirms that scurvy is associated with poor dietary habits
      and low socio-economic status leading to inadequate vitamin C intake."
treatments:
- name: Vitamin C Supplementation
  description: >
    Oral vitamin C supplementation (100-300 mg daily) rapidly reverses symptoms.
    Clinical improvement typically begins within 24-48 hours. The condition can be
    adequately treated and prevented via vitamin C supplementation.
  treatment_term:
    preferred_term: vitamin C supplementation
    term:
      id: MAXO:0000109
      label: vitamin C supplementation
  evidence:
  - reference: PMID:37366866
    reference_title: "Scurvy: Rediscovering a Forgotten Disease."
    supports: SUPPORT
    snippet: "It can be adequately treated and prevented via vitamin C supplementation."
    explanation: "This confirms that vitamin C supplementation is the adequate treatment
      and prevention for scurvy."
notes: |
  Scurvy is a historically significant disease that affected sailors on long voyages
  before the discovery of vitamin C's role. It is now rare in developed countries but
  can occur in individuals with severely restricted diets, alcoholism, or malabsorption
  disorders. The disease is completely reversible with vitamin C replacement.
references:
- reference: DOI:10.1007/s40124-024-00315-9
  title: 'Vitamin C: Is it Relevant or Obsolete in the Modern Era?'
  findings: []
- reference: DOI:10.1016/j.cardiores.2006.05.005
  title: Regulating cellular oxygen sensing by hydroxylation
  findings: []
- reference: DOI:10.1038/s41598-024-56326-5
  title: The level of active DNA demethylation compounds in leukocytes and urine
    samples as potential epigenetic biomarkers in breast cancer patients
  findings: []
- reference: DOI:10.1093/nar/gkac941
  title: Vitamin C enhances NF-κB-driven epigenomic reprogramming and boosts the
    immunogenic properties of dendritic cells
  findings: []
- reference: DOI:10.1182/blood.2019004158
  title: TET family dioxygenases and the TET activator vitamin C in immune
    responses and cancer
  findings: []
- reference: DOI:10.1186/s12888-020-02730-w
  title: 'The neuropsychiatric effects of vitamin C deficiency: a systematic review'
  findings: []
- reference: DOI:10.3389/fnut.2023.1265334
  title: 'Scurvy in a young man: a rare case report'
  findings: []
- reference: DOI:10.3390/diseases11020078
  title: 'Scurvy: Rediscovering a Forgotten Disease'
  findings: []
- reference: DOI:10.3390/molecules30030748
  title: 'Vitamin C: A Comprehensive Review of Its Role in Health, Disease Prevention,
    and Therapeutic Potential'
  findings: []
- reference: DOI:10.37275/bsm.v8i9.1066
  title: 'Analysis of the Role of Vitamin C Hypovitaminosis in Scurvy on Bone Health:
    A Single Center Observational Study at Dr. Moewardi General Hospital, Surakarta,
    Indonesia'
  findings: []
📚

References & Deep Research

References

10
DOI:10.1007/s40124-024-00315-9
Vitamin C: Is it Relevant or Obsolete in the Modern Era?
No top-level findings curated for this source.
DOI:10.1016/j.cardiores.2006.05.005
Regulating cellular oxygen sensing by hydroxylation
No top-level findings curated for this source.
DOI:10.1038/s41598-024-56326-5
The level of active DNA demethylation compounds in leukocytes and urine samples as potential epigenetic biomarkers in breast cancer patients
No top-level findings curated for this source.
DOI:10.1093/nar/gkac941
Vitamin C enhances NF-κB-driven epigenomic reprogramming and boosts the immunogenic properties of dendritic cells
No top-level findings curated for this source.
DOI:10.1182/blood.2019004158
TET family dioxygenases and the TET activator vitamin C in immune responses and cancer
No top-level findings curated for this source.
DOI:10.1186/s12888-020-02730-w
The neuropsychiatric effects of vitamin C deficiency: a systematic review
No top-level findings curated for this source.
DOI:10.3389/fnut.2023.1265334
Scurvy in a young man: a rare case report
No top-level findings curated for this source.
DOI:10.3390/diseases11020078
Scurvy: Rediscovering a Forgotten Disease
No top-level findings curated for this source.
DOI:10.3390/molecules30030748
Vitamin C: A Comprehensive Review of Its Role in Health, Disease Prevention, and Therapeutic Potential
No top-level findings curated for this source.
DOI:10.37275/bsm.v8i9.1066
Analysis of the Role of Vitamin C Hypovitaminosis in Scurvy on Bone Health: A Single Center Observational Study at Dr. Moewardi General Hospital, Surakarta, Indonesia
No top-level findings curated for this source.

Deep Research

2
Disorder ▸

Disorder

  • Name: Scurvy
  • Category: Nutritional
  • Existing deep-research providers: falcon
  • Existing evidence reference count in YAML: 24

Key Pathophysiology Nodes

  • Collagen Synthesis Impairment
  • Vascular Integrity Failure
  • Deep research literature mapping

Citation Inventory (for evidence mapping)

  • DOI:10.1007/s40124-024-00315-9
  • DOI:10.1016/j.cardiores.2006.05.005
  • DOI:10.1038/s41598-024-56326-5
  • DOI:10.1093/nar/gkac941
  • DOI:10.1182/blood.2019004158
  • DOI:10.1186/s12888-020-02730-w
  • DOI:10.3389/fnut.2023.1265334
  • DOI:10.3390/diseases11020078
  • DOI:10.3390/molecules30030748
  • DOI:10.37275/bsm.v8i9.1066
Falcon ▸
Pathophysiology description (concise overview)
Edison Scientific Literature 23 citations 2026-01-08T14:22:44.926520

Pathophysiology description (concise overview)

Scurvy results from inadequate L-ascorbate (vitamin C), an essential reducing cofactor for multiple non-heme Fe(II)/2-oxoglutarate (2-OG)–dependent dioxygenases and select monooxygenases. The cardinal molecular lesion is failure of collagen post-translational hydroxylation (proline, lysine), which destabilizes the triple helix, impairs cross-linking, and weakens extracellular matrix (ECM). Clinically, this manifests as capillary fragility with bleeding (petechiae, ecchymoses, gingival hemorrhage), poor wound healing, musculoskeletal pain, and characteristic bone/growth plate abnormalities. Ascorbate also supports HIF hydroxylases (EGLN/PHDs, FIH), TET DNA demethylases, dopamine β-hydroxylase (DBH), peptidylglycine α-amidating monooxygenase (PAM), and carnitine biosynthesis, so deficiency can secondarily perturb hypoxia signaling, epigenetic regulation, catecholamine and peptide amidation pathways, and cellular energy metabolism. Tissue vitamin C homeostasis depends on SLC23A1/SLC23A2 (SVCT1/2) and complementary uptake of dehydroascorbic acid (DHA) via GLUT transporters; dietary lack depletes the small total body pool within weeks, producing the clinical picture of scurvy (gastrointestinal and systemic bleeding, mucocutaneous and skeletal features). (gandhi2023scurvyrediscoveringa pages 1-2, gandhi2023scurvyrediscoveringa pages 2-4, ramanujan2024vitamincis pages 7-7)

1. Core Pathophysiology

  • Collagen hydroxylation failure • Ascorbate donates electrons to prolyl and lysyl hydroxylases during collagen biosynthesis; without ascorbate, hydroxyproline/4-hydroxylysine formation is inadequate, preventing triple-helix stability and mature cross-links. “This reaction uses ascorbic acid as an electron donor,” and failure of hydroxylation impairs bone and fibroblast function, tooth development, wound healing, and vessel integrity. (Gandhi 2023, Diseases, May 2023; doi:10.3390/diseases11020078; https://doi.org/10.3390/diseases11020078) (gandhi2023scurvyrediscoveringa pages 2-4)
  • ECM and vascular integrity • Matrix failure in skin and mucosa explains perifollicular hemorrhage, petechiae, ecchymoses, gingival swelling/bleeding, and gastrointestinal bleeding with normal coagulation tests in many patients. (Gandhi 2023) (gandhi2023scurvyrediscoveringa pages 1-2, gandhi2023scurvyrediscoveringa pages 4-5)
  • Bone and growth plate • Deficient osteoid formation and increased bone resorption yield osteopenia/osteoporosis, cortical thinning, metaphyseal changes and growth-plate abnormalities; pediatric scurvy often presents with limb pain, limp or refusal to walk, and characteristic radiologic bands and periosteal changes. (Gandhi 2023; Lu 2023, Front Nutr, Oct 2023; doi:10.3389/fnut.2023.1265334; https://doi.org/10.3389/fnut.2023.1265334) (gandhi2023scurvyrediscoveringa pages 4-5, lu2023scurvyina pages 2-3)
  • Hypoxia/epigenetic enzyme effects • Ascorbate supports Fe(II)/2-OG dioxygenases beyond collagen: HIF prolyl hydroxylases (EGLN1/2/3) and the asparaginyl hydroxylase FIH regulate HIF; ascorbate helps maintain their catalytic cycles, so deficiency can dysregulate HIF activity. TET dioxygenases (TET1–3) require ascorbate to promote DNA demethylation; low vitamin C may contribute to aberrant methylation. (Fandrey 2006, Cardiovasc Res, Sep 2006; doi:10.1016/j.cardiores.2006.05.005; https://doi.org/10.1016/j.cardiores.2006.05.005; Yue & Rao 2020, Blood, Sep 2020; doi:10.1182/blood.2019004158; https://doi.org/10.1182/blood.2019004158) (ramanujan2024vitamincis pages 7-7, alberts2025vitaminca pages 1-2)
  • Neurochemical and energy pathways • DBH uses ascorbate to convert dopamine to norepinephrine; vitamin C deficiency therefore can lower NE synthesis, contributing to fatigue, mood/cognitive symptoms and autonomic complaints. Ascorbate also serves as electron donor for carnitine biosynthesis steps; deficiency can reduce carnitine availability and worsen fatigue. (Gandhi 2023; Plevin & Galletly 2020, BMC Psychiatry, Jun 2020; doi:10.1186/s12888-020-02730-w; https://doi.org/10.1186/s12888-020-02730-w) (gandhi2023scurvyrediscoveringa pages 2-4, gandhi2023scurvyrediscoveringa pages 4-5)

2. Key Molecular Players

  • Genes/Proteins (HGNC): Prolyl 4-hydroxylase (P4HA1/2/3); Lysyl hydroxylase (PLOD1/2/3); EGLN1/2/3 (PHD1–3); HIF1AN (FIH); TET1/2/3; DBH; PAM; TMLHE/BBOX1 (carnitine biosynthesis); SLC23A1/2 (SVCT1/2); SLC2A family (GLUTs for DHA). Mechanistic roles and evidence mapping are synthesized in the artifact below. (ramanujan2024vitamincis pages 7-7, gandhi2023scurvyrediscoveringa pages 2-4, alberts2025vitaminca pages 1-2)
  • Chemical Entities (CHEBI): L‑ascorbate; dehydroascorbic acid; dopamine; norepinephrine; carnitine. (gandhi2023scurvyrediscoveringa pages 2-4, lu2023scurvyina pages 2-3)
  • Cell Types (CL): Fibroblasts (collagen production), endothelial cells (capillary integrity), osteoblasts and chondrocytes (osteoid and growth plate matrix). (gandhi2023scurvyrediscoveringa pages 4-5)
  • Anatomical Locations (UBERON): Skin, gingiva, bone, epiphyseal (growth) plate, GI mucosa. (gandhi2023scurvyrediscoveringa pages 4-5, gandhi2023scurvyrediscoveringa pages 1-2)
Category Entity Name Ontology ID / Abbrev Role in Scurvy Pathophysiology (1-2 sentences) Evidence
Enzyme Prolyl 4-hydroxylase alpha subunits (P4HA1/2/3) HGNC:P4HA1/P4HA2/P4HA3 Hydroxylate proline residues in procollagen to enable triple-helix formation; impaired activity from ascorbate deficiency destabilizes collagen and weakens ECM, causing bleeding and poor wound healing. (ramanujan2024vitamincis pages 7-7, gandhi2023scurvyrediscoveringa pages 2-4)
Enzyme Lysyl hydroxylases (PLOD1/2/3) HGNC:PLOD1/PLOD2/PLOD3 Hydroxylate lysine residues required for collagen cross-linking; deficiency reduces crosslinks leading to fragile connective tissue and defective bone matrix. (ramanujan2024vitamincis pages 7-7, gandhi2023scurvyrediscoveringa pages 2-4)
Enzyme (oxygen sensor) HIF prolyl hydroxylases (EGLN1/2/3, a.k.a. PHD1/2/3) HGNC:EGLN1/EGLN2/EGLN3 2‑OG/Fe(II)-dependent prolyl hydroxylases that regulate HIF stability; ascorbate maintains enzyme activity so deficiency can dysregulate hypoxia signaling. (ramanujan2024vitamincis pages 7-7)
Enzyme (regulator) Factor inhibiting HIF (HIF1AN / FIH) HGNC:HIF1AN Asparaginyl hydroxylase that modulates HIF transcriptional activity; requires reducing cofactor activity supported by ascorbate, so deficiency can alter HIF transcriptional outputs. (ramanujan2024vitamincis pages 7-7)
Enzyme (epigenetic) TET1 / TET2 / TET3 HGNC:TET1/TET2/TET3 Fe(II)/2‑OG dioxygenases that oxidize 5mC to 5hmC promoting active DNA demethylation; ascorbate is a cofactor and deficiency may impair epigenetic regulation. (alberts2025vitaminca pages 1-2, gandhi2023scurvyrediscoveringa pages 2-4)
Enzyme (catecholamine) Dopamine beta-hydroxylase (DBH) HGNC:DBH Converts dopamine → norepinephrine within secretory vesicles using ascorbate as electron donor; deficiency can reduce NE synthesis and contribute to neuropsychiatric/autonomic features. (gandhi2023scurvyrediscoveringa pages 2-4, ramanujan2024vitamincis pages 7-7)
Enzyme (peptide maturation) Peptidylglycine alpha-amidating monooxygenase (PAM) HGNC:PAM Amidating monooxygenase requiring ascorbate for peptide hormone/neuropeptide maturation; deficiency may impair peptide signaling. (gandhi2023scurvyrediscoveringa pages 2-4, ramanujan2024vitamincis pages 7-7)
Enzymes (carnitine biosynthesis) TMLHE, BBOX1 HGNC:TMLHE, BBOX1 Ascorbate-dependent dioxygenase steps in carnitine biosynthesis; deficiency can reduce carnitine levels and contribute to muscle fatigue. (gandhi2023scurvyrediscoveringa pages 2-4, lu2023scurvyina pages 2-3)
Transporter Vitamin C transporters (SLC23A1 / SLC23A2; SVCT1/2) HGNC:SLC23A1, SLC23A2 Sodium-dependent vitamin C transporters mediate ascorbate uptake and tissue accumulation; altered expression or saturation affects tissue ascorbate and scurvy susceptibility. (ramanujan2024vitamincis pages 7-7)
Transporter (alternative) DHA transport via GLUTs (SLC2A family) HGNC:SLC2A* (GLUTs) Oxidized form dehydroascorbic acid (DHA) can be transported via GLUT family members and reduced intracellularly to ascorbate, providing an alternative uptake route. (gandhi2023scurvyrediscoveringa pages 2-4, ramanujan2024vitamincis pages 7-7)
Structural protein / GO Collagen (generic) GO:0005581 (extracellular matrix) Principal ECM protein requiring prolyl/lysyl hydroxylation for structural stability; defective collagen underlies capillary fragility, mucosal bleeding, poor wound healing, and defective bone matrix. (gandhi2023scurvyrediscoveringa pages 2-4, lu2023scurvyina pages 2-3)
Cell type (CL) Fibroblast CL:Fibroblast Major collagen-producing stromal cell; impaired collagen processing in fibroblasts leads to weakened dermal and connective tissues seen in scurvy. (gandhi2023scurvyrediscoveringa pages 2-4, ramanujan2024vitamincis pages 7-7)
Cell type (CL) Osteoblast CL:Osteoblast Bone-forming cells that produce osteoid rich in type I collagen; defective collagen synthesis impairs osteoid formation, causing osteoporosis, cortical thinning, and growth-plate pathology. (gandhi2023scurvyrediscoveringa pages 4-5, nefihancoro2024analysisofthe pages 4-7)
Cell type (CL) Chondrocyte CL:Chondrocyte Cartilage/growth-plate cells that depend on collagen-rich matrix; ascorbate deficiency impairs endochondral matrix formation producing metaphyseal and epiphyseal abnormalities. (gandhi2023scurvyrediscoveringa pages 4-5, lu2023scurvyina pages 2-3)
Cell type (CL) Endothelial cell CL:Endothelial cell Vascular integrity relies on collagen-containing basement membrane; impaired collagen leads to capillary fragility and hemorrhage (petechiae, ecchymoses). (gandhi2023scurvyrediscoveringa pages 2-4, gandhi2023scurvyrediscoveringa pages 1-2)
Anatomy (UBERON) Gingiva UBERON:Gingiva Highly vascular mucosa with collagen-rich stroma; scurvy causes gingival swelling, bleeding, and periodontal disease due to ECM failure. (gandhi2023scurvyrediscoveringa pages 2-4, lu2023scurvyina pages 2-3)
Anatomy (UBERON) Skin UBERON:Skin Dermal ECM failure causes perifollicular hemorrhages, petechiae, and poor wound healing characteristic of scurvy. (gandhi2023scurvyrediscoveringa pages 4-5, gandhi2023scurvyrediscoveringa pages 2-4)
Anatomy (UBERON) Bone UBERON:Bone Impaired collagen in osteoid leads to brittle bones, osteoporosis, cortical thinning, and fracture risk in scurvy. (nefihancoro2024analysisofthe pages 4-7, gandhi2023scurvyrediscoveringa pages 4-5)
Anatomy (UBERON) Epiphyseal (growth) plate UBERON:Epiphyseal_plate Collagen-dependent cartilage zone for endochondral ossification; deficiency produces growth-plate abnormalities, metaphyseal bands, and limp/pseudoparalysis in children. (gandhi2023scurvyrediscoveringa pages 4-5, lu2023scurvyina pages 2-3)
Chemical (CHEBI) L-ascorbate (vitamin C) CHEBI:Asc Essential reducing cofactor for multiple Fe(II)/2‑OG dioxygenases and antioxidant; insufficient levels cause scurvy. (gandhi2023scurvyrediscoveringa pages 1-2, ramanujan2024vitamincis pages 7-7)
Chemical (CHEBI) Dehydroascorbic acid (DHA) CHEBI:DHA Oxidized form of ascorbate transported via GLUTs and reduced intracellularly to regenerate ascorbate; important alternative uptake pathway. (gandhi2023scurvyrediscoveringa pages 2-4, ramanujan2024vitamincis pages 7-7)
Chemical (CHEBI) Dopamine CHEBI:Dopamine Catecholamine precursor converted by DBH to norepinephrine using ascorbate; impaired DBH activity can alter neurotransmitter balance. (gandhi2023scurvyrediscoveringa pages 2-4, ramanujan2024vitamincis pages 7-7)
Chemical (CHEBI) Norepinephrine CHEBI:Norepinephrine Product of DBH; reduced synthesis in severe ascorbate deficiency may contribute to autonomic and neuropsychiatric symptoms. (gandhi2023scurvyrediscoveringa pages 2-4, ramanujan2024vitamincis pages 7-7)
Chemical (CHEBI) Carnitine CHEBI:Carnitine Requires ascorbate-dependent enzymatic steps for biosynthesis; deficiency can impair fatty acid transport into mitochondria and produce fatigue/weakness. (gandhi2023scurvyrediscoveringa pages 2-4, lu2023scurvyina pages 2-3)

Table: A concise reference table mapping enzymes, cells, tissues, and chemicals relevant to scurvy to ontology identifiers, their roles in pathophysiology, and the supporting evidence (context IDs). This facilitates ontology-driven annotation and rapid linking of mechanisms to sources.

3. Biological Processes (GO) disrupted

  • Collagen biosynthetic process and post-translational modification (proline/lysine hydroxylation; triple-helix formation; cross-linking); ECM organization; wound healing; angiogenesis and vascular integrity. (Gandhi 2023) (gandhi2023scurvyrediscoveringa pages 2-4, gandhi2023scurvyrediscoveringa pages 4-5)
  • Cellular responses to hypoxia; regulation of HIF signaling by prolyl/asparaginyl hydroxylation (EGLN/PHDs; FIH). (Fandrey 2006) (ramanujan2024vitamincis pages 7-7)
  • DNA demethylation via TET-mediated oxidation of 5-mC to 5-hmC; epigenetic regulation of immune and lineage programs. (Yue & Rao 2020; Morante-Palacios 2022, Nucleic Acids Res, Oct 2022; doi:10.1093/nar/gkac941; https://doi.org/10.1093/nar/gkac941) (alberts2025vitaminca pages 1-2, ramanujan2024vitamincis pages 7-8)
  • Catecholamine biosynthetic process (DBH step dopamine→norepinephrine); peptide amidation (PAM); carnitine biosynthetic process. (Gandhi 2023; Plevin 2020) (gandhi2023scurvyrediscoveringa pages 2-4, gandhi2023scurvyrediscoveringa pages 4-5)

4. Cellular Components affected

  • Endoplasmic reticulum lumen and cisternae (collagen prolyl/lysyl hydroxylases act co-translationally/post-translationally on procollagen); secretory pathway/extracellular space (ECM deposition). (Gandhi 2023) (gandhi2023scurvyrediscoveringa pages 2-4)
  • Nucleus/chromatin (TET-mediated DNA demethylation); cytosol and mitochondria (carnitine metabolism); secretory vesicles (DBH in catecholaminergic vesicles). (Yue 2020; Plevin 2020) (alberts2025vitaminca pages 1-2, gandhi2023scurvyrediscoveringa pages 4-5)

5. Disease Progression

  • Trigger and depletion: Humans lack GULO and must ingest vitamin C; limited body pool (approx. 1–3 weeks to deplete on very low intake) and saturable gut/renal handling cause rapid deficiency under poor diet/malabsorption. (Gandhi 2023) (gandhi2023scurvyrediscoveringa pages 1-2)
  • Early biochemical failure: Insufficient ascorbate disrupts collagen hydroxylation, compromising ECM repair and capillary integrity; fatigue may occur early via reduced catecholamines and carnitine. (Lu 2023; Gandhi 2023) (lu2023scurvyina pages 2-3, gandhi2023scurvyrediscoveringa pages 2-4)
  • Clinical evolution: Within 4–12 weeks of inadequate intake, nonspecific symptoms progress to gingival bleeding, perifollicular hemorrhages, ecchymoses, joint pain/hemarthrosis, and in children, limb pain and refusal to walk due to metaphyseal and periosteal changes. (Gandhi 2023) (gandhi2023scurvyrediscoveringa pages 4-5)
  • Advanced skeletal involvement: Osteoporosis and cortical thinning correlate with severity; growth-plate pathology and fractures may occur if untreated. (Nefihancoro 2024, Bioscientia Medicina, Jun 2024; doi:10.37275/bsm.v8i9.1066; https://doi.org/10.37275/bsm.v8i9.1066) (nefihancoro2024analysisofthe pages 4-7)
  • Reversibility: Vitamin C repletion rapidly reverses constitutional and bleeding symptoms; musculoskeletal recovery follows over weeks. (Lu 2023) (lu2023scurvyina pages 2-3)

6. Phenotypic Manifestations and mechanistic links

  • Mucocutaneous: Perifollicular hemorrhages, petechiae, ecchymoses, corkscrew hairs, gingival swelling/bleeding—due to fragile capillaries and ECM failure from defective collagen. (Gandhi 2023) (gandhi2023scurvyrediscoveringa pages 4-5)
  • Musculoskeletal: Arthralgias, hemarthrosis, muscle hematomas; in children, limp/refusal to walk; radiologic metaphyseal bands, periosteal reaction, and osteopenia—reflecting defective osteoid/calcified cartilage matrix. (Gandhi 2023) (gandhi2023scurvyrediscoveringa pages 4-5)
  • Gastrointestinal: Occult or overt bleeding due to mucosal/vascular fragility. (Gandhi 2023) (gandhi2023scurvyrediscoveringa pages 1-2)
  • Neuropsychiatric: Fatigue, depression, cognitive complaints are reported in deficiency; biologically linked to decreased NE synthesis (DBH cofactor role) and broader neurotransmitter/antioxidant roles. (Plevin 2020) (gandhi2023scurvyrediscoveringa pages 4-5)

Evidence items (with selected direct quotations)

  • “This reaction uses ascorbic acid as an electron donor,” referring to hydroxylation of proline and lysine residues in collagen; failure of hydroxylation impairs bone and fibroblast function, tooth development, wound healing, and vessel integrity. (Gandhi 2023, Diseases, May 2023; https://doi.org/10.3390/diseases11020078) (gandhi2023scurvyrediscoveringa pages 2-4)
  • Pediatric skeletal presentation: review and MRI/radiograph features (periosteal reaction, metaphyseal bands, refusal to walk) summarized in Gandhi 2023. (gandhi2023scurvyrediscoveringa pages 4-5)
  • Observational 2024 bone study: “Radiological examination shows significant changes in long bones, especially osteoporosis and thinning of the cortex... positive correlation between the severity of scurvy and the incidence of osteoporosis (rho = 0.495, p = 0.005) and cortical thinning (rho = 0.394, p = 0.031).” (Nefihancoro 2024; https://doi.org/10.37275/bsm.v8i9.1066) (nefihancoro2024analysisofthe pages 4-7)
  • TET and vitamin C: Vitamin C “serves as a cofactor for Fe(II) and 2-oxoglutarate (2OG)-dependent dioxygenases including TET family enzymes,” promoting DNA demethylation. (Yue & Rao 2020, Blood; https://doi.org/10.1182/blood.2019004158) (alberts2025vitaminca pages 1-2)
  • HIF hydroxylases: Mechanistic role of ascorbate in preserving prolyl hydroxylase activity and regulating HIF signaling reviewed by Fandrey et al. (Cardiovasc Res 2006; https://doi.org/10.1016/j.cardiores.2006.05.005) (ramanujan2024vitamincis pages 7-7)
  • Immune/epigenetic reprogramming: Vitamin C enhances NF-κB–driven epigenomic remodeling in dendritic cells via TET2, boosting antigen presentation. (Morante‑Palacios 2022; https://doi.org/10.1093/nar/gkac941) (ramanujan2024vitamincis pages 7-8)

Current applications and real‑world implementations

  • Clinical detection and radiology • Recent case reports and observational data (2023–2024) emphasize that scurvy should be considered in patients with unexplained mucocutaneous bleeding and musculoskeletal pain; radiographs/MRI can reveal metaphyseal bands, periosteal reactions, osteopenia, and cortical thinning that improve with repletion. (Lu 2023; Nefihancoro 2024) (lu2023scurvyina pages 2-3, nefihancoro2024analysisofthe pages 4-7)
  • Risk stratification and transporters • Contemporary pediatric review synthesizes transporter biology (SLC23A1/2; DHA uptake via GLUTs) and vulnerable populations (e.g., chronic disease, critical illness), informing screening and supplementation strategies. (Ramanujan 2024, Curr Pediatr Rep, May 2024; https://doi.org/10.1007/s40124-024-00315-9) (ramanujan2024vitamincis pages 7-8, ramanujan2024vitamincis pages 7-7)

Expert opinions and analysis

  • Consensus from recent reviews supports a central role for ascorbate in collagen hydroxylation and broader dioxygenase biology, with clinical scurvy arising from ECM failure and secondarily from dysregulated hypoxia and epigenetic pathways in some contexts. (Gandhi 2023; Ramanujan 2024; Yue 2020) (gandhi2023scurvyrediscoveringa pages 2-4, ramanujan2024vitamincis pages 7-8, alberts2025vitaminca pages 1-2)
  • The 2024 observational bone study underscores that scurvy still presents with significant skeletal morbidity; systematic radiological assessment and prompt vitamin C repletion can mitigate complications. (Nefihancoro 2024) (nefihancoro2024analysisofthe pages 4-7)

Relevant statistics and data (recent)

  • Nefihancoro 2024 (Indonesia, 2020–2023; n=30): fatigue 86.7%, joint pain 73.3%, bleeding gums 60%, skin bleeding 53.3%; radiology showed osteoporosis and cortical thinning with severity; Spearman correlations: osteoporosis rho=0.495 (p=0.005), cortical thinning rho=0.394 (p=0.031). (https://doi.org/10.37275/bsm.v8i9.1066) (nefihancoro2024analysisofthe pages 4-7)
  • Pediatric presentation patterns summarized across recent literature (limp/refusal to walk ~one-third; musculoskeletal complaints ~90% in children). (Gandhi 2023) (gandhi2023scurvyrediscoveringa pages 4-5)

Gene/protein annotations with ontology terms

  • HGNC: P4HA1/2/3; PLOD1/2/3; EGLN1/2/3; HIF1AN; TET1/2/3; DBH; PAM; TMLHE; BBOX1; SLC23A1/SLC23A2; SLC2A family. (ramanujan2024vitamincis pages 7-7, alberts2025vitaminca pages 1-2)
  • GO processes: collagen biosynthetic process; extracellular matrix organization; wound healing; response to hypoxia; DNA demethylation; catecholamine biosynthetic process; peptide amidation; carnitine biosynthetic process. (gandhi2023scurvyrediscoveringa pages 2-4, ramanujan2024vitamincis pages 7-7, alberts2025vitaminca pages 1-2)
  • Cellular components: endoplasmic reticulum lumen; secretory vesicle; extracellular matrix; chromatin. (gandhi2023scurvyrediscoveringa pages 2-4, alberts2025vitaminca pages 1-2)

Phenotype associations (HP terms; narrative mapping)

  • Mucocutaneous bleeding (petechiae, ecchymoses), gingival hypertrophy/bleeding, poor wound healing, perifollicular hemorrhages; musculoskeletal pain/hemarthrosis; pediatric limp/refusal to walk; osteopenia/osteoporosis; cortical thinning; metaphyseal bands and periosteal reaction on imaging. Mechanistic links: collagen hydroxylation failure → ECM weakness and capillary fragility; impaired osteoid matrix. (gandhi2023scurvyrediscoveringa pages 4-5, nefihancoro2024analysisofthe pages 4-7)

Cell type involvement (CL terms; narrative mapping)

  • Fibroblasts (dermal ECM); endothelial cells (capillary walls); osteoblasts and chondrocytes (bone/growth plate matrix); immune dendritic cells (ascorbate-dependent TET reprogramming). (gandhi2023scurvyrediscoveringa pages 4-5, ramanujan2024vitamincis pages 7-8)

Anatomical locations (UBERON; narrative mapping)

  • Skin, gingiva, bone, epiphyseal (growth) plate, gastrointestinal mucosa. (gandhi2023scurvyrediscoveringa pages 4-5, gandhi2023scurvyrediscoveringa pages 1-2)

Chemical entities (CHEBI; narrative mapping)

  • L‑ascorbate, dehydroascorbic acid (DHA), dopamine, norepinephrine, carnitine. (gandhi2023scurvyrediscoveringa pages 2-4, lu2023scurvyina pages 2-3)

Transport and tissue distribution

  • Active intestinal uptake and renal handling are saturable; dehydroascorbic acid can “passively penetrate cellular membranes” and is preferentially taken up by erythrocytes and leukocytes (DHA → ascorbate intracellular reduction). SLC23A1/SLC23A2 (SVCT1/2) underlie systemic/tissue accumulation; decreased plasma ascorbate with compensatory changes in SLC23A1/2 expression is observed in disease states, underscoring reliance on these transporters. (Gandhi 2023; Ramanujan 2024; Linowiecka 2024, Sci Rep, Mar 2024; doi:10.1038/s41598-024-56326-5; https://doi.org/10.1038/s41598-024-56326-5) (gandhi2023scurvyrediscoveringa pages 2-4, ramanujan2024vitamincis pages 7-8, ramanujan2024vitamincis pages 7-7)

References with URLs and dates (selected)

  • Gandhi M et al. Scurvy: Rediscovering a Forgotten Disease. Diseases. May 2023. doi:10.3390/diseases11020078. https://doi.org/10.3390/diseases11020078 (gandhi2023scurvyrediscoveringa pages 1-2, gandhi2023scurvyrediscoveringa pages 2-4, gandhi2023scurvyrediscoveringa pages 4-5)
  • Lu R-L et al. Scurvy in a young man: a rare case report. Front Nutr. Oct 2023. doi:10.3389/fnut.2023.1265334. https://doi.org/10.3389/fnut.2023.1265334 (lu2023scurvyina pages 2-3)
  • Nefihancoro UH, Faisal R. Analysis of the Role of Vitamin C Hypovitaminosis in Scurvy on Bone Health. Bioscientia Medicina. Jun 2024. doi:10.37275/bsm.v8i9.1066. https://doi.org/10.37275/bsm.v8i9.1066 (nefihancoro2024analysisofthe pages 4-7)
  • Ramanujan S et al. Vitamin C: Is it Relevant or Obsolete in the Modern Era? Curr Pediatr Rep. May 2024. doi:10.1007/s40124-024-00315-9. https://doi.org/10.1007/s40124-024-00315-9 (ramanujan2024vitamincis pages 7-8, ramanujan2024vitamincis pages 7-7)
  • Yue X, Rao A. TET family dioxygenases and the TET activator vitamin C in immune responses and cancer. Blood. Sep 2020. doi:10.1182/blood.2019004158. https://doi.org/10.1182/blood.2019004158 (alberts2025vitaminca pages 1-2)
  • Morante‑Palacios O et al. Vitamin C enhances NF‑κB‑driven epigenomic reprogramming… Nucleic Acids Res. Oct 2022. doi:10.1093/nar/gkac941. https://doi.org/10.1093/nar/gkac941 (ramanujan2024vitamincis pages 7-8)
  • Fandrey J et al. Regulating cellular oxygen sensing by hydroxylation. Cardiovasc Res. Sep 2006. doi:10.1016/j.cardiores.2006.05.005. https://doi.org/10.1016/j.cardiores.2006.05.005 (ramanujan2024vitamincis pages 7-7)
  • Plevin D, Galletly C. The neuropsychiatric effects of vitamin C deficiency: a systematic review. BMC Psychiatry. Jun 2020. doi:10.1186/s12888-020-02730-w. https://doi.org/10.1186/s12888-020-02730-w (gandhi2023scurvyrediscoveringa pages 4-5)

Notes on evidence strength and recency: We prioritized 2023–2024 clinical and review literature for modern presentations and radiologic skeletal data (Gandhi 2023; Lu 2023; Nefihancoro 2024; Ramanujan 2024). Mechanistic underpinnings referencing ascorbate’s enzymology and transporter biology are supported by these recent reviews and by established mechanistic reviews on HIF/TET dioxygenases (Fandrey 2006; Yue 2020; Morante‑Palacios 2022). Where possible, we included direct quotations for key mechanistic claims and provided DOI/URL and publication dates. (gandhi2023scurvyrediscoveringa pages 2-4, nefihancoro2024analysisofthe pages 4-7, ramanujan2024vitamincis pages 7-8, alberts2025vitaminca pages 1-2, ramanujan2024vitamincis pages 7-7)

References

  1. (gandhi2023scurvyrediscoveringa pages 1-2): Mustafa Gandhi, Omar Elfeky, Hamza Ertugrul, Harleen Kaur Chela, and Ebubekir Daglilar. Scurvy: rediscovering a forgotten disease. Diseases, 11:78, May 2023. URL: https://doi.org/10.3390/diseases11020078, doi:10.3390/diseases11020078. This article has 82 citations and is from a poor quality or predatory journal.

  2. (gandhi2023scurvyrediscoveringa pages 2-4): Mustafa Gandhi, Omar Elfeky, Hamza Ertugrul, Harleen Kaur Chela, and Ebubekir Daglilar. Scurvy: rediscovering a forgotten disease. Diseases, 11:78, May 2023. URL: https://doi.org/10.3390/diseases11020078, doi:10.3390/diseases11020078. This article has 82 citations and is from a poor quality or predatory journal.

  3. (ramanujan2024vitamincis pages 7-7): Suruchi Ramanujan, Sanu Yadav, Andrea Adler, Sara Bewley, and Kadakkal Radhakrishnan. Vitamin c: is it relevant or obsolete in the modern era? Current Pediatrics Reports, 12:35-43, May 2024. URL: https://doi.org/10.1007/s40124-024-00315-9, doi:10.1007/s40124-024-00315-9. This article has 6 citations.

  4. (gandhi2023scurvyrediscoveringa pages 4-5): Mustafa Gandhi, Omar Elfeky, Hamza Ertugrul, Harleen Kaur Chela, and Ebubekir Daglilar. Scurvy: rediscovering a forgotten disease. Diseases, 11:78, May 2023. URL: https://doi.org/10.3390/diseases11020078, doi:10.3390/diseases11020078. This article has 82 citations and is from a poor quality or predatory journal.

  5. (lu2023scurvyina pages 2-3): Rui-Ling Lu, Jie-Wen Guo, Bao-dong Sun, Yu-Lan Chen, and Dong-Zhou Liu. Scurvy in a young man: a rare case report. Frontiers in Nutrition, Oct 2023. URL: https://doi.org/10.3389/fnut.2023.1265334, doi:10.3389/fnut.2023.1265334. This article has 7 citations and is from a poor quality or predatory journal.

  6. (alberts2025vitaminca pages 1-2): Adina Alberts, Elena-Theodora Moldoveanu, Adelina-Gabriela Niculescu, and Alexandru Mihai Grumezescu. Vitamin c: a comprehensive review of its role in health, disease prevention, and therapeutic potential. Molecules, 30:748, Feb 2025. URL: https://doi.org/10.3390/molecules30030748, doi:10.3390/molecules30030748. This article has 75 citations and is from a poor quality or predatory journal.

  7. (nefihancoro2024analysisofthe pages 4-7): Udi Heru Nefihancoro and Rachmad Faisal. Analysis of the role of vitamin c hypovitaminosis in scurvy on bone health: a single center observational study at dr. moewardi general hospital, surakarta, indonesia. Bioscientia Medicina : Journal of Biomedicine and Translational Research, 8:4894-4902, Jun 2024. URL: https://doi.org/10.37275/bsm.v8i9.1066, doi:10.37275/bsm.v8i9.1066. This article has 0 citations.

  8. (ramanujan2024vitamincis pages 7-8): Suruchi Ramanujan, Sanu Yadav, Andrea Adler, Sara Bewley, and Kadakkal Radhakrishnan. Vitamin c: is it relevant or obsolete in the modern era? Current Pediatrics Reports, 12:35-43, May 2024. URL: https://doi.org/10.1007/s40124-024-00315-9, doi:10.1007/s40124-024-00315-9. This article has 6 citations.