L-Ascorbic acid

availability_state

biomarker_context Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/copper-research/3694287.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "37e70fcbc672023cd6c3616b4a1171c6ded4caafe4e3c14d4f80c6abca490e68", "start_char": 0, "end_char": 1031, "text_sha256": "37e70fcbc672023cd6c3616b4a1171c6ded4caafe4e3c14d4f80c6abca490e68"}

experimental_model

Controlled sequential dietary vitamin C intervention

exposure

Fourteen-week feeding study: 65, 5, 605 and 5 mg vitamin C/day in successive periods

limitations

Short sequential study; ceruloplasmin activity differs from protein concentration and whole-body copper stores. No universal vitamin C threshold is established.

nutrient_topic

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

organism

Human men

plain_language

The activity change did not demonstrate loss of body copper.

primary_references

[copper-p3694287] Effect of varying ascorbic acid intakes on copper absorption and ceruloplasmin levels of young men. (1987). https://pubmed.ncbi.nlm.nih.gov/3694287/ DOI: 10.1093/jn/117.12.2109

tissue_or_cell_type

Copper absorption, retention and circulating markers

trigger_kind

biomarker_context Imported condition classification; unverified.

Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 1118–1129

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Controlled sequential dietary vitamin C intervention · source_derived_draft · unverified_draft

### copper-ascorbate-copper-retention The study found no significant vitamin-C-period effect on copper absorption, retention, serum copper or ceruloplasmin protein despite the oxidase-activity change. Condition category: biomarker_context nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: The activity change did not demonstrate loss of body copper. organism: Human men tissue_or_cell_type: Copper absorption, retention and circulating markers experimental_model: Controlled sequential dietary vitamin C intervention limitations: Short sequential study; ceruloplasmin activity differs from protein concentration and whole-body copper stores. No universal vitamin C threshold is established. exposure: Fourteen-week feeding study: 65, 5, 605 and 5 mg vitamin C/day in successive periods evidence_span: {"source_cache": "artifacts/copper-research/3694287.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "37e70fcbc672023cd6c3616b4a1171c6ded4caafe4e3c14d4f80c6abca490e68", "start_char": 0, "end_char": 1031, "text_sha256": "37e70fcbc672023cd6c3616b4a1171c6ded4caafe4e3c14d4f80c6abca490e68"} [copper-p3694287] Effect of varying ascorbic acid intakes on copper absorption and ceruloplasmin levels of young men. (1987). https://pubmed.ncbi.nlm.nih.gov/3694287/ DOI: 10.1093/jn/117.12.2109

availability_state

biomarker_context Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/copper-research/3694287.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "37e70fcbc672023cd6c3616b4a1171c6ded4caafe4e3c14d4f80c6abca490e68", "start_char": 0, "end_char": 1031, "text_sha256": "37e70fcbc672023cd6c3616b4a1171c6ded4caafe4e3c14d4f80c6abca490e68"}

experimental_model

Controlled sequential dietary vitamin C intervention

exposure

Fourteen-week feeding study: 65, 5, 605 and 5 mg vitamin C/day in successive periods

limitations

Short sequential study; ceruloplasmin activity differs from protein concentration and whole-body copper stores. No universal vitamin C threshold is established.

nutrient_topic

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

organism

Human men

plain_language

A copper-related enzyme measurement changed with vitamin C intake.

primary_references

[copper-p3694287] Effect of varying ascorbic acid intakes on copper absorption and ceruloplasmin levels of young men. (1987). https://pubmed.ncbi.nlm.nih.gov/3694287/ DOI: 10.1093/jn/117.12.2109

tissue_or_cell_type

Copper absorption, retention and circulating markers

trigger_kind

biomarker_context Imported condition classification; unverified.

Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 1105–1116

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Controlled sequential dietary vitamin C intervention · source_derived_draft · unverified_draft

### copper-ascorbate-cp-oxidase The 605 mg/day vitamin C period reduced ceruloplasmin oxidase activity by about 21% in the controlled feeding study. Condition category: biomarker_context nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: A copper-related enzyme measurement changed with vitamin C intake. organism: Human men tissue_or_cell_type: Copper absorption, retention and circulating markers experimental_model: Controlled sequential dietary vitamin C intervention limitations: Short sequential study; ceruloplasmin activity differs from protein concentration and whole-body copper stores. No universal vitamin C threshold is established. exposure: Fourteen-week feeding study: 65, 5, 605 and 5 mg vitamin C/day in successive periods evidence_span: {"source_cache": "artifacts/copper-research/3694287.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "37e70fcbc672023cd6c3616b4a1171c6ded4caafe4e3c14d4f80c6abca490e68", "start_char": 0, "end_char": 1031, "text_sha256": "37e70fcbc672023cd6c3616b4a1171c6ded4caafe4e3c14d4f80c6abca490e68"} [copper-p3694287] Effect of varying ascorbic acid intakes on copper absorption and ceruloplasmin levels of young men. (1987). https://pubmed.ncbi.nlm.nih.gov/3694287/ DOI: 10.1093/jn/117.12.2109

availability_state

biomarker_context Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/copper-research/6837490.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "628dd5cb00ff83cf6d31ff973073a19041de727a370d8652715bb6452b29bc03", "start_char": 0, "end_char": 1026, "text_sha256": "628dd5cb00ff83cf6d31ff973073a19041de727a370d8652715bb6452b29bc03"}

experimental_model

Within-person vitamin C supplementation and withdrawal study

exposure

1500 mg vitamin C/day for 64 days on self-selected diets

limitations

No independent placebo control; measured values remained within cited physiological ranges, and serum copper decline during supplementation was not significant.

nutrient_topic

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

organism

Human men

plain_language

Enzyme activity was more responsive than the copper concentration measurement in this small study.

primary_references

[copper-p6837490] Influence of ascorbic acid supplementation on copper status in young adult men. (1983). https://pubmed.ncbi.nlm.nih.gov/6837490/ DOI: 10.1093/ajcn/37.4.553

tissue_or_cell_type

Circulating copper and ceruloplasmin activity

trigger_kind

biomarker_context Imported condition classification; unverified.

Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 1131–1142

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Within-person vitamin C supplementation and withdrawal study · source_derived_draft · unverified_draft

### copper-high-vitc-cp-activity Ceruloplasmin oxidase activity decreased during 1500 mg/day vitamin C supplementation; the serum copper decline was not statistically significant. Condition category: biomarker_context nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Enzyme activity was more responsive than the copper concentration measurement in this small study. organism: Human men tissue_or_cell_type: Circulating copper and ceruloplasmin activity experimental_model: Within-person vitamin C supplementation and withdrawal study limitations: No independent placebo control; measured values remained within cited physiological ranges, and serum copper decline during supplementation was not significant. exposure: 1500 mg vitamin C/day for 64 days on self-selected diets evidence_span: {"source_cache": "artifacts/copper-research/6837490.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "628dd5cb00ff83cf6d31ff973073a19041de727a370d8652715bb6452b29bc03", "start_char": 0, "end_char": 1026, "text_sha256": "628dd5cb00ff83cf6d31ff973073a19041de727a370d8652715bb6452b29bc03"} [copper-p6837490] Influence of ascorbic acid supplementation on copper status in young adult men. (1983). https://pubmed.ncbi.nlm.nih.gov/6837490/ DOI: 10.1093/ajcn/37.4.553

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/copper-research/3337044.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2302118b1dad186fdee87512abf58f47a36d430e329057c87b24e57e52e331cc", "start_char": 0, "end_char": 882, "text_sha256": "2302118b1dad186fdee87512abf58f47a36d430e329057c87b24e57e52e331cc"}

experimental_model

Factorial dietary copper, iron and ascorbate feeding experiment

exposure

Copper 0.42 versus 5.74 micrograms/g diet; iron 38 versus 191 micrograms/g; ascorbate 0 versus 1%, for 20 days

limitations

Animal feed concentrations cannot be converted into a human supplement rule. Baseline copper status modified effects.

nutrient_topic

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

organism

Rat

plain_language

A nutrient combination worsened the deficit in this animal setting.

primary_references

[copper-p3337044] Adverse effects of high dietary iron and ascorbic acid on copper status in copper-deficient and copper-adequate rats. (1988). https://pubmed.ncbi.nlm.nih.gov/3337044/ DOI: 10.1093/ajcn/47.1.96

tissue_or_cell_type

Intestinal uptake, blood and tissues

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 1157–1168

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Factorial dietary copper, iron and ascorbate feeding experiment · source_derived_draft · unverified_draft

### copper-iron-vitc-lowcu-anemia High iron together with dietary ascorbate aggravated anemia in copper-deficient rats. Condition category: nutrient_deficiency nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: A nutrient combination worsened the deficit in this animal setting. organism: Rat tissue_or_cell_type: Intestinal uptake, blood and tissues experimental_model: Factorial dietary copper, iron and ascorbate feeding experiment limitations: Animal feed concentrations cannot be converted into a human supplement rule. Baseline copper status modified effects. exposure: Copper 0.42 versus 5.74 micrograms/g diet; iron 38 versus 191 micrograms/g; ascorbate 0 versus 1%, for 20 days evidence_span: {"source_cache": "artifacts/copper-research/3337044.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2302118b1dad186fdee87512abf58f47a36d430e329057c87b24e57e52e331cc", "start_char": 0, "end_char": 882, "text_sha256": "2302118b1dad186fdee87512abf58f47a36d430e329057c87b24e57e52e331cc"} [copper-p3337044] Adverse effects of high dietary iron and ascorbic acid on copper status in copper-deficient and copper-adequate rats. (1988). https://pubmed.ncbi.nlm.nih.gov/3337044/ DOI: 10.1093/ajcn/47.1.96

dose

Eugenol with peroxidase/hydrogen peroxide plus ascorbate or glutathione

duration

Acute

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Cell-free peroxidase systems and human HL-60 cells

limitations

Cell-free protection does not prove that vitamin supplementation prevents toxicity in exposed humans.

nutrient_topic

Eugenol chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Eugenol

organism

Cell-free peroxidase systems and human HL-60 cells

plain_language

Ascorbic acid and glutathione reduced DNA-adduct formation during in-vitro peroxidase activation of eugenol by about 66% and 90%, respectively.

primary_references

Oxidation of eugenol to form DNA adducts and 8-hydroxy-2'-deoxyguanosine: role of quinone methide derivative in DNA adduct formation. (1998). https://pubmed.ncbi.nlm.nih.gov/9525278/ DOI: 10.1093/carcin/19.3.437

route

In vitro

tissue

DNA adducts and oxidative base damage

Eugenol: mechanism of action and interactions (2026-09-20) · lines 121–130

Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · Cell-free peroxidase systems and human HL-60 cells · source_derived_draft · unverified_draft

## eugenol-ascorbate-gsh-adduct-protection Ascorbic acid and glutathione reduced DNA-adduct formation during in-vitro peroxidase activation of eugenol by about 66% and 90%, respectively. Model/species: Cell-free peroxidase systems and human HL-60 cells Tissue/system: DNA adducts and oxidative base damage Exposure: Eugenol with peroxidase/hydrogen peroxide plus ascorbate or glutathione Route: In vitro Duration: Acute Limits: Cell-free protection does not prove that vitamin supplementation prevents toxicity in exposed humans. Primary reference: Oxidation of eugenol to form DNA adducts and 8-hydroxy-2'-deoxyguanosine: role of quinone methide derivative in DNA adduct formation. (1998). https://pubmed.ncbi.nlm.nih.gov/9525278/ DOI: 10.1093/carcin/19.3.437 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

true

experimental_model

Same-genotype nutritional comparison and bisulfite sequencing

exposure

Gulo-null dams: water vitamin C withdrawn 3-7 days before mating through E13.5; controls 3.3 g/L.

limitations

Methylation-expression association does not prove the sole causal mediator or impaired RA synthesis.

nutrient_topic

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

organism

Mus musculus

plain_language

Vitamin C shortage altered an epigenetic step in germ-cell development.

primary_references

[ditroia2019] Maternal vitamin C regulates reprogramming of DNA methylation and germline development. (2019). https://pubmed.ncbi.nlm.nih.gov/31485074/ DOI: 10.1038/s41586-019-1536-1

tissue_or_cell_type

female fetal germ cells

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Vitamin A expansion: reproduction, light-driven vision and shared mechanisms (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 · Same-genotype nutritional comparison and bisulfite sequencing · source_derived_draft · unverified_draft

### va-repro-vitamin-c-demethylation Maternal vitamin C withdrawal increased Dazl-promoter methylation in female fetal germ cells, with reduced Dazl expression. Condition category: nutrient_deficiency nutrient_topic: Vitamin A expansion research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin C shortage altered an epigenetic step in germ-cell development. organism: Mus musculus tissue_or_cell_type: female fetal germ cells experimental_model: Same-genotype nutritional comparison and bisulfite sequencing limitations: Methylation-expression association does not prove the sole causal mediator or impaired RA synthesis. exposure: Gulo-null dams: water vitamin C withdrawn 3-7 days before mating through E13.5; controls 3.3 g/L. cross_nutrient: true [ditroia2019] Maternal vitamin C regulates reprogramming of DNA methylation and germline development. (2019). https://pubmed.ncbi.nlm.nih.gov/31485074/ DOI: 10.1038/s41586-019-1536-1

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

true

experimental_model

Nutrient withdrawal with histology and meiotic staging

exposure

Withdrawal before mating through E13.5; same-genotype supplemented controls; staging at E14.5.

limitations

The individual SYCP3-positive protein fraction was not significantly reduced; this is not an A-C supplementation trial.

nutrient_topic

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

organism

Mus musculus

plain_language

A second nutrient shortage affected the germ-cell program also studied in vitamin A biology.

primary_references

[ditroia2019] Maternal vitamin C regulates reprogramming of DNA methylation and germline development. (2019). https://pubmed.ncbi.nlm.nih.gov/31485074/ DOI: 10.1038/s41586-019-1536-1

tissue_or_cell_type

female fetal ovary

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Vitamin A expansion: reproduction, light-driven vision and shared mechanisms (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 · Nutrient withdrawal with histology and meiotic staging · source_derived_draft · unverified_draft

### va-repro-vitamin-c-meiotic-delay Maternal vitamin C deficiency delayed female fetal meiotic progression, with reduced STRA8 expression. Condition category: nutrient_deficiency nutrient_topic: Vitamin A expansion research collection; topical membership is not evidence of a direct dietary effect. plain_language: A second nutrient shortage affected the germ-cell program also studied in vitamin A biology. organism: Mus musculus tissue_or_cell_type: female fetal ovary experimental_model: Nutrient withdrawal with histology and meiotic staging limitations: The individual SYCP3-positive protein fraction was not significantly reduced; this is not an A-C supplementation trial. exposure: Withdrawal before mating through E13.5; same-genotype supplemented controls; staging at E14.5. cross_nutrient: true [ditroia2019] Maternal vitamin C regulates reprogramming of DNA methylation and germline development. (2019). https://pubmed.ncbi.nlm.nih.gov/31485074/ DOI: 10.1038/s41586-019-1536-1

experimental_model

Seven healthy volunteers hospitalized for 4–6 months in a controlled depletion/repletion study.

exposure

Diet below 5 mg vitamin C/day, followed by seven daily doses spanning 30–2500 mg; separate single-dose bioavailability assessments.

limitations

Distinguish fraction absorbed from absolute amount and single-dose results from daily steady-state dosing.

nutrient_topic

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

organism

Homo sapiens

plain_language

A larger swallowed dose did not mean the same fraction entered circulation.

primary_references

[c-levine1996] Vitamin C pharmacokinetics in healthy volunteers: evidence for a recommended dietary allowance (1996). https://pubmed.ncbi.nlm.nih.gov/8623000/ DOI: 10.1073/pnas.93.8.3704

tissue_or_cell_type

Human blood or whole-person endpoints

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1421–1431

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Seven healthy volunteers hospitalized for 4–6 months in a controlled depletion/repletion study. · source_derived_draft · unverified_draft

### c-bioavailability-dose-dependence A 200-mg single dose had complete bioavailability; fractional bioavailability declined at single doses of 500 mg and above. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: A larger swallowed dose did not mean the same fraction entered circulation. organism: Homo sapiens tissue_or_cell_type: Human blood or whole-person endpoints experimental_model: Seven healthy volunteers hospitalized for 4–6 months in a controlled depletion/repletion study. limitations: Distinguish fraction absorbed from absolute amount and single-dose results from daily steady-state dosing. exposure: Diet below 5 mg vitamin C/day, followed by seven daily doses spanning 30–2500 mg; separate single-dose bioavailability assessments. [c-levine1996] Vitamin C pharmacokinetics in healthy volunteers: evidence for a recommended dietary allowance (1996). https://pubmed.ncbi.nlm.nih.gov/8623000/ DOI: 10.1073/pnas.93.8.3704

experimental_model

CITRIS-ALI: double-blind multicenter randomized trial; 170 initially randomized, three subsequently excluded without receiving C, 167 in the reported analysis (84 C, 83 placebo).

exposure

IV vitamin C 50 mg/kg in 5% dextrose every six hours for 96 hours versus dextrose placebo.

limitations

Marker results do not establish that every inflammatory pathway was unchanged.

nutrient_topic

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

organism

Homo sapiens

plain_language

This inflammatory marker did not show the proposed benefit.

primary_references

[c-fowler2019] Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure: The CITRIS-ALI Randomized Clinical Trial (2019). https://pubmed.ncbi.nlm.nih.gov/31573637/ DOI: 10.1001/jama.2019.11825

tissue_or_cell_type

Human blood or whole-person endpoints

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1731–1741

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · CITRIS-ALI: double-blind multicenter randomized trial; 170 initially randomized, three subsequently excluded without receiving C, 167 in the reported analysis (84 C, 83 placebo). · source_derived_draft · unverified_draft

### c-citris-crp-null At 168 hours, the prespecified CRP comparison was nonsignificant (P=0.33). Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: This inflammatory marker did not show the proposed benefit. organism: Homo sapiens tissue_or_cell_type: Human blood or whole-person endpoints experimental_model: CITRIS-ALI: double-blind multicenter randomized trial; 170 initially randomized, three subsequently excluded without receiving C, 167 in the reported analysis (84 C, 83 placebo). limitations: Marker results do not establish that every inflammatory pathway was unchanged. exposure: IV vitamin C 50 mg/kg in 5% dextrose every six hours for 96 hours versus dextrose placebo. [c-fowler2019] Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure: The CITRIS-ALI Randomized Clinical Trial (2019). https://pubmed.ncbi.nlm.nih.gov/31573637/ DOI: 10.1001/jama.2019.11825

experimental_model

CITRIS-ALI: double-blind multicenter randomized trial; 170 initially randomized, three subsequently excluded without receiving C, 167 in the reported analysis (84 C, 83 placebo).

exposure

IV vitamin C 50 mg/kg in 5% dextrose every six hours for 96 hours versus dextrose placebo.

limitations

One of 46 secondary outcomes; 43 were nonsignificant. Different eligibility and endpoint hierarchy from LOVIT. The signal is hypothesis-generating, and no cellular mediator was proven.

nutrient_topic

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

organism

Homo sapiens

plain_language

This smaller trial reported a possible survival benefit, although its main endpoints were negative.

primary_references

[c-fowler2019] Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure: The CITRIS-ALI Randomized Clinical Trial (2019). https://pubmed.ncbi.nlm.nih.gov/31573637/ DOI: 10.1001/jama.2019.11825

tissue_or_cell_type

Human blood or whole-person endpoints

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1755–1765

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · CITRIS-ALI: double-blind multicenter randomized trial; 170 initially randomized, three subsequently excluded without receiving C, 167 in the reported analysis (84 C, 83 placebo). · source_derived_draft · unverified_draft

### c-citris-exploratory-mortality-signal Day-28 mortality was 25/84 (29.8%) with C versus 38/82 (46.3%) with placebo (P=0.03), in an exploratory analysis without adjustment for multiple comparisons. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: This smaller trial reported a possible survival benefit, although its main endpoints were negative. organism: Homo sapiens tissue_or_cell_type: Human blood or whole-person endpoints experimental_model: CITRIS-ALI: double-blind multicenter randomized trial; 170 initially randomized, three subsequently excluded without receiving C, 167 in the reported analysis (84 C, 83 placebo). limitations: One of 46 secondary outcomes; 43 were nonsignificant. Different eligibility and endpoint hierarchy from LOVIT. The signal is hypothesis-generating, and no cellular mediator was proven. exposure: IV vitamin C 50 mg/kg in 5% dextrose every six hours for 96 hours versus dextrose placebo. [c-fowler2019] Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure: The CITRIS-ALI Randomized Clinical Trial (2019). https://pubmed.ncbi.nlm.nih.gov/31573637/ DOI: 10.1001/jama.2019.11825

experimental_model

CITRIS-ALI: double-blind multicenter randomized trial; 170 initially randomized, three subsequently excluded without receiving C, 167 in the reported analysis (84 C, 83 placebo).

exposure

IV vitamin C 50 mg/kg in 5% dextrose every six hours for 96 hours versus dextrose placebo.

limitations

This specific primary endpoint is not a summary of every secondary outcome.

nutrient_topic

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

organism

Homo sapiens

plain_language

The studied infusion did not improve the trial’s main organ-function score.

primary_references

[c-fowler2019] Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure: The CITRIS-ALI Randomized Clinical Trial (2019). https://pubmed.ncbi.nlm.nih.gov/31573637/ DOI: 10.1001/jama.2019.11825

tissue_or_cell_type

Human blood or whole-person endpoints

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1719–1729

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · CITRIS-ALI: double-blind multicenter randomized trial; 170 initially randomized, three subsequently excluded without receiving C, 167 in the reported analysis (84 C, 83 placebo). · source_derived_draft · unverified_draft

### c-citris-organ-score-null CITRIS-ALI found no significant difference in the primary modified SOFA change through 96 hours (P=0.86). Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: The studied infusion did not improve the trial’s main organ-function score. organism: Homo sapiens tissue_or_cell_type: Human blood or whole-person endpoints experimental_model: CITRIS-ALI: double-blind multicenter randomized trial; 170 initially randomized, three subsequently excluded without receiving C, 167 in the reported analysis (84 C, 83 placebo). limitations: This specific primary endpoint is not a summary of every secondary outcome. exposure: IV vitamin C 50 mg/kg in 5% dextrose every six hours for 96 hours versus dextrose placebo. [c-fowler2019] Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure: The CITRIS-ALI Randomized Clinical Trial (2019). https://pubmed.ncbi.nlm.nih.gov/31573637/ DOI: 10.1001/jama.2019.11825

experimental_model

CITRIS-ALI: double-blind multicenter randomized trial; 170 initially randomized, three subsequently excluded without receiving C, 167 in the reported analysis (84 C, 83 placebo).

exposure

IV vitamin C 50 mg/kg in 5% dextrose every six hours for 96 hours versus dextrose placebo.

limitations

The circulating marker is distinct from directly measuring endothelial repair.

nutrient_topic

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

organism

Homo sapiens

plain_language

This vessel-injury marker did not show the proposed benefit.

primary_references

[c-fowler2019] Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure: The CITRIS-ALI Randomized Clinical Trial (2019). https://pubmed.ncbi.nlm.nih.gov/31573637/ DOI: 10.1001/jama.2019.11825

tissue_or_cell_type

Human blood or whole-person endpoints

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1743–1753

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · CITRIS-ALI: double-blind multicenter randomized trial; 170 initially randomized, three subsequently excluded without receiving C, 167 in the reported analysis (84 C, 83 placebo). · source_derived_draft · unverified_draft

### c-citris-thrombomodulin-null At 168 hours, the prespecified thrombomodulin comparison was nonsignificant (P=0.70). Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: This vessel-injury marker did not show the proposed benefit. organism: Homo sapiens tissue_or_cell_type: Human blood or whole-person endpoints experimental_model: CITRIS-ALI: double-blind multicenter randomized trial; 170 initially randomized, three subsequently excluded without receiving C, 167 in the reported analysis (84 C, 83 placebo). limitations: The circulating marker is distinct from directly measuring endothelial repair. exposure: IV vitamin C 50 mg/kg in 5% dextrose every six hours for 96 hours versus dextrose placebo. [c-fowler2019] Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure: The CITRIS-ALI Randomized Clinical Trial (2019). https://pubmed.ncbi.nlm.nih.gov/31573637/ DOI: 10.1001/jama.2019.11825

cross_nutrient

Clinical outcome boundary for extrapolation from vitamin C/vitamin E redox recycling.

experimental_model

Physicians Health Study II: placebo-controlled double-blind factorial trial, 14641 male physicians aged at least 50, mean eight-year follow-up.

exposure

Vitamin C 500 mg/day and separately randomized vitamin E 400 IU every other day; clinical CVD endpoints.

limitations

Older male physicians, not a selected scurvy cohort; separate vitamin E randomization is not proof of molecular synergy or antagonism.

nutrient_topic

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

organism

Homo sapiens

plain_language

A long-term supplement trial did not turn the antioxidant rationale into fewer major cardiovascular events.

primary_references

[c-sesso2008] Vitamins E and C in the prevention of cardiovascular disease in men: the Physicians' Health Study II randomized controlled trial (2008). https://pubmed.ncbi.nlm.nih.gov/18997197/ DOI: 10.1001/jama.2008.600

tissue_or_cell_type

Human blood or whole-person endpoints

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1830–1841

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Physicians Health Study II: placebo-controlled double-blind factorial trial, 14641 male physicians aged at least 50, mean eight-year follow-up. · source_derived_draft · unverified_draft

### c-cvd-prevention-null Vitamin C assignment did not reduce major cardiovascular events (HR 0.99; 95% CI 0.89–1.11; P=0.91) over mean eight-year follow-up. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: A long-term supplement trial did not turn the antioxidant rationale into fewer major cardiovascular events. organism: Homo sapiens tissue_or_cell_type: Human blood or whole-person endpoints experimental_model: Physicians Health Study II: placebo-controlled double-blind factorial trial, 14641 male physicians aged at least 50, mean eight-year follow-up. limitations: Older male physicians, not a selected scurvy cohort; separate vitamin E randomization is not proof of molecular synergy or antagonism. exposure: Vitamin C 500 mg/day and separately randomized vitamin E 400 IU every other day; clinical CVD endpoints. cross_nutrient: Clinical outcome boundary for extrapolation from vitamin C/vitamin E redox recycling. [c-sesso2008] Vitamins E and C in the prevention of cardiovascular disease in men: the Physicians' Health Study II randomized controlled trial (2008). https://pubmed.ncbi.nlm.nih.gov/18997197/ DOI: 10.1001/jama.2008.600

cross_nutrient

Calcium/oxalate urinary chemistry connects a vitamin metabolite to mineral precipitation risk.

experimental_model

Randomized controlled-diet crossover study: 29 calcium stone formers and 19 non-stone formers.

exposure

Ascorbic acid 1000 mg twice daily for six days versus no supplement for six days; 13C2 oxalate challenge after adaptation.

limitations

Calculated risk is not observed stone formation; this is distinct from a directly measured calcium oxalate activity product.

nutrient_topic

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

organism

Homo sapiens

plain_language

Their urine measurements shifted toward a higher calculated calcium oxalate stone risk.

primary_references

[c-massey2005] Ascorbate increases human oxaluria and kidney stone risk (2005). https://pubmed.ncbi.nlm.nih.gov/15987848/ DOI: 10.1093/jn/135.7.1673

tissue_or_cell_type

Human blood or whole-person endpoints

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1682–1693

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized controlled-diet crossover study: 29 calcium stone formers and 19 non-stone formers. · source_derived_draft · unverified_draft

### c-high-oral-dose-calcium-oxalate-index The responder subset had a Tiselius Risk Index of 1.10 with versus 0.76 without supplementation. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Their urine measurements shifted toward a higher calculated calcium oxalate stone risk. organism: Homo sapiens tissue_or_cell_type: Human blood or whole-person endpoints experimental_model: Randomized controlled-diet crossover study: 29 calcium stone formers and 19 non-stone formers. limitations: Calculated risk is not observed stone formation; this is distinct from a directly measured calcium oxalate activity product. exposure: Ascorbic acid 1000 mg twice daily for six days versus no supplement for six days; 13C2 oxalate challenge after adaptation. cross_nutrient: Calcium/oxalate urinary chemistry connects a vitamin metabolite to mineral precipitation risk. [c-massey2005] Ascorbate increases human oxaluria and kidney stone risk (2005). https://pubmed.ncbi.nlm.nih.gov/15987848/ DOI: 10.1093/jn/135.7.1673

experimental_model

Randomized controlled-diet crossover study: 29 calcium stone formers and 19 non-stone formers.

exposure

Ascorbic acid 1000 mg twice daily for six days versus no supplement for six days; 13C2 oxalate challenge after adaptation.

limitations

Not a universal effect in all 48 participants; intestinal mediator was not identified.

nutrient_topic

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

organism

Homo sapiens

plain_language

The additional urinary oxalate was not attributed solely to vitamin C breakdown.

primary_references

[c-massey2005] Ascorbate increases human oxaluria and kidney stone risk (2005). https://pubmed.ncbi.nlm.nih.gov/15987848/ DOI: 10.1093/jn/135.7.1673

tissue_or_cell_type

Human blood or whole-person endpoints

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1670–1680

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized controlled-diet crossover study: 29 calcium stone formers and 19 non-stone formers. · source_derived_draft · unverified_draft

### c-high-oral-dose-oxalate-absorption Responder-subset dietary oxalate absorption was 10.5% versus 8.0% with versus without vitamin C. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: The additional urinary oxalate was not attributed solely to vitamin C breakdown. organism: Homo sapiens tissue_or_cell_type: Human blood or whole-person endpoints experimental_model: Randomized controlled-diet crossover study: 29 calcium stone formers and 19 non-stone formers. limitations: Not a universal effect in all 48 participants; intestinal mediator was not identified. exposure: Ascorbic acid 1000 mg twice daily for six days versus no supplement for six days; 13C2 oxalate challenge after adaptation. [c-massey2005] Ascorbate increases human oxaluria and kidney stone risk (2005). https://pubmed.ncbi.nlm.nih.gov/15987848/ DOI: 10.1093/jn/135.7.1673

experimental_model

Randomized controlled-diet crossover study: 29 calcium stone formers and 19 non-stone formers.

exposure

Ascorbic acid 1000 mg twice daily for six days versus no supplement for six days; 13C2 oxalate challenge after adaptation.

limitations

Selected subgroup and short exposure; does not identify every enzymatic or nonenzymatic conversion step.

nutrient_topic

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

organism

Homo sapiens

plain_language

The tracer-based analysis separated oxalate made within the body from oxalate absorbed from the test diet.

primary_references

[c-massey2005] Ascorbate increases human oxaluria and kidney stone risk (2005). https://pubmed.ncbi.nlm.nih.gov/15987848/ DOI: 10.1093/jn/135.7.1673

tissue_or_cell_type

Human blood or whole-person endpoints

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1658–1668

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized controlled-diet crossover study: 29 calcium stone formers and 19 non-stone formers. · source_derived_draft · unverified_draft

### c-high-oral-dose-oxalate-synthesis Within the responder subset, estimated endogenous oxalate synthesis was 544 versus 391 micromol/day with versus without supplementation. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: The tracer-based analysis separated oxalate made within the body from oxalate absorbed from the test diet. organism: Homo sapiens tissue_or_cell_type: Human blood or whole-person endpoints experimental_model: Randomized controlled-diet crossover study: 29 calcium stone formers and 19 non-stone formers. limitations: Selected subgroup and short exposure; does not identify every enzymatic or nonenzymatic conversion step. exposure: Ascorbic acid 1000 mg twice daily for six days versus no supplement for six days; 13C2 oxalate challenge after adaptation. [c-massey2005] Ascorbate increases human oxaluria and kidney stone risk (2005). https://pubmed.ncbi.nlm.nih.gov/15987848/ DOI: 10.1093/jn/135.7.1673

cross_nutrient

Oxalate is relevant to calcium oxalate stone chemistry.

experimental_model

Randomized controlled-diet crossover study: 29 calcium stone formers and 19 non-stone formers.

exposure

Ascorbic acid 1000 mg twice daily for six days versus no supplement for six days; 13C2 oxalate challenge after adaptation.

limitations

Responders were defined by the observed rise; no incident-stone endpoint and no extrapolation to ordinary food intake.

nutrient_topic

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

organism

Homo sapiens

plain_language

Some people excreted more oxalate after the high oral exposure.

primary_references

[c-massey2005] Ascorbate increases human oxaluria and kidney stone risk (2005). https://pubmed.ncbi.nlm.nih.gov/15987848/ DOI: 10.1093/jn/135.7.1673

tissue_or_cell_type

Human blood or whole-person endpoints

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1645–1656

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized controlled-diet crossover study: 29 calcium stone formers and 19 non-stone formers. · source_derived_draft · unverified_draft

### c-high-oral-dose-oxaluria Nineteen of 48 participants, including 12 stone formers and seven non-stone formers, had more than 10% greater 24-hour oxalate excretion with 2 g/day vitamin C. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Some people excreted more oxalate after the high oral exposure. organism: Homo sapiens tissue_or_cell_type: Human blood or whole-person endpoints experimental_model: Randomized controlled-diet crossover study: 29 calcium stone formers and 19 non-stone formers. limitations: Responders were defined by the observed rise; no incident-stone endpoint and no extrapolation to ordinary food intake. exposure: Ascorbic acid 1000 mg twice daily for six days versus no supplement for six days; 13C2 oxalate challenge after adaptation. cross_nutrient: Oxalate is relevant to calcium oxalate stone chemistry. [c-massey2005] Ascorbate increases human oxaluria and kidney stone risk (2005). https://pubmed.ncbi.nlm.nih.gov/15987848/ DOI: 10.1093/jn/135.7.1673

cross_nutrient

Direct vitamin C/iron transport experiment.

experimental_model

Differentiated human Caco-2 monolayers; apical ferric nitrilotriacetate and transepithelial transport assays.

exposure

Apical 10 micromolar Fe(III) as 1 Fe:2 NTA, varied ascorbic acid, ascorbate oxidase and Fe(II) chelators.

limitations

Culture concentrations and ligand system cannot be converted into a human absorption percentage.

nutrient_topic

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

organism

Homo sapiens

plain_language

More iron crossed the model cell layer under those experimental conditions.

primary_references

[c-han1995] Reduction of Fe(III) is required for uptake of nonheme iron by Caco-2 cells (1995). https://pubmed.ncbi.nlm.nih.gov/7738689/ DOI: 10.1093/jn/125.5.1291

tissue_or_cell_type

Human Caco-2 monolayers

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1567–1578

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Differentiated human Caco-2 monolayers; apical ferric nitrilotriacetate and transepithelial transport assays. · source_derived_draft · unverified_draft

### c-iron-transepithelial-flux Apical ascorbic acid at 100 and 1000 micromolar increased apical-to-basolateral iron transport 5.6-fold and 30-fold, respectively, in the ferric-NTA system. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: More iron crossed the model cell layer under those experimental conditions. organism: Homo sapiens tissue_or_cell_type: Human Caco-2 monolayers experimental_model: Differentiated human Caco-2 monolayers; apical ferric nitrilotriacetate and transepithelial transport assays. limitations: Culture concentrations and ligand system cannot be converted into a human absorption percentage. exposure: Apical 10 micromolar Fe(III) as 1 Fe:2 NTA, varied ascorbic acid, ascorbate oxidase and Fe(II) chelators. cross_nutrient: Direct vitamin C/iron transport experiment. [c-han1995] Reduction of Fe(III) is required for uptake of nonheme iron by Caco-2 cells (1995). https://pubmed.ncbi.nlm.nih.gov/7738689/ DOI: 10.1093/jn/125.5.1291

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Vitamin C/iron clinical outcome recorded separately from the uptake reaction.

experimental_model

Single-center open-label randomized equivalence trial: 440 adults with iron-deficiency anemia, 426 women.

exposure

Ferrous succinate 100 mg/tablet with or without vitamin C 200 mg every eight hours, three months; taken half an hour after meals. Tablet mass is not relabeled as elemental iron.

limitations

Ferritin is a biomarker; no proof that iron absorption was identical at every meal.

nutrient_topic

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

organism

Homo sapiens

plain_language

The added vitamin C did not significantly improve the measured iron-storage response.

primary_references

[c-li2020] The Efficacy and Safety of Vitamin C for Iron Supplementation in Adult Patients With Iron Deficiency Anemia: A Randomized Clinical Trial (2020). https://pubmed.ncbi.nlm.nih.gov/33136134/ DOI: 10.1001/jamanetworkopen.2020.23644

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 1632–1643

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Single-center open-label randomized equivalence trial: 440 adults with iron-deficiency anemia, 426 women. · source_derived_draft · unverified_draft

### c-iron-treatment-ferritin-null Eight-week ferritin increases were 35.75 versus 34.48 ng/mL; between-group difference 1.27 (95% CI -0.70 to 3.24; P=0.21). Condition category: nutrient_deficiency nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: The added vitamin C did not significantly improve the measured iron-storage response. organism: Homo sapiens tissue_or_cell_type: Human blood or whole-person endpoints experimental_model: Single-center open-label randomized equivalence trial: 440 adults with iron-deficiency anemia, 426 women. limitations: Ferritin is a biomarker; no proof that iron absorption was identical at every meal. exposure: Ferrous succinate 100 mg/tablet with or without vitamin C 200 mg every eight hours, three months; taken half an hour after meals. Tablet mass is not relabeled as elemental iron. cross_nutrient: Vitamin C/iron clinical outcome recorded separately from the uptake reaction. [c-li2020] The Efficacy and Safety of Vitamin C for Iron Supplementation in Adult Patients With Iron Deficiency Anemia: A Randomized Clinical Trial (2020). https://pubmed.ncbi.nlm.nih.gov/33136134/ DOI: 10.1001/jamanetworkopen.2020.23644

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Separates chemical absorption support from added clinical benefit during iron replacement.

experimental_model

Single-center open-label randomized equivalence trial: 440 adults with iron-deficiency anemia, 426 women.

exposure

Ferrous succinate 100 mg/tablet with or without vitamin C 200 mg every eight hours, three months; taken half an hour after meals. Tablet mass is not relabeled as elemental iron.

limitations

Equivalence is margin-dependent and does not mean numerical identity; no direct isotope absorption or intracellular mechanism was measured.

nutrient_topic

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

organism

Homo sapiens

plain_language

Adding vitamin C did not provide a clinically distinct early hemoglobin response under the trial’s equivalence definition.

primary_references

[c-li2020] The Efficacy and Safety of Vitamin C for Iron Supplementation in Adult Patients With Iron Deficiency Anemia: A Randomized Clinical Trial (2020). https://pubmed.ncbi.nlm.nih.gov/33136134/ DOI: 10.1001/jamanetworkopen.2020.23644

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 1619–1630

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Single-center open-label randomized equivalence trial: 440 adults with iron-deficiency anemia, 426 women. · source_derived_draft · unverified_draft

### c-iron-treatment-hemoglobin-equivalence Hemoglobin increased 2.00 g/dL with iron plus C versus 1.84 with iron alone at two weeks; difference 0.16 (95% CI -0.03 to 0.35), within the prespecified 1-g/dL equivalence margin. Condition category: nutrient_deficiency nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Adding vitamin C did not provide a clinically distinct early hemoglobin response under the trial’s equivalence definition. organism: Homo sapiens tissue_or_cell_type: Human blood or whole-person endpoints experimental_model: Single-center open-label randomized equivalence trial: 440 adults with iron-deficiency anemia, 426 women. limitations: Equivalence is margin-dependent and does not mean numerical identity; no direct isotope absorption or intracellular mechanism was measured. exposure: Ferrous succinate 100 mg/tablet with or without vitamin C 200 mg every eight hours, three months; taken half an hour after meals. Tablet mass is not relabeled as elemental iron. cross_nutrient: Separates chemical absorption support from added clinical benefit during iron replacement. [c-li2020] The Efficacy and Safety of Vitamin C for Iron Supplementation in Adult Patients With Iron Deficiency Anemia: A Randomized Clinical Trial (2020). https://pubmed.ncbi.nlm.nih.gov/33136134/ DOI: 10.1001/jamanetworkopen.2020.23644

experimental_model

Seven healthy volunteers hospitalized for 4–6 months in a controlled depletion/repletion study.

exposure

Diet below 5 mg vitamin C/day, followed by seven daily doses spanning 30–2500 mg; separate single-dose bioavailability assessments.

limitations

Concentration is not an immune-function or infection-prevention endpoint.

nutrient_topic

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

organism

Homo sapiens

plain_language

Blood cells can concentrate vitamin C; the surrounding plasma does not give the same number.

primary_references

[c-levine1996] Vitamin C pharmacokinetics in healthy volunteers: evidence for a recommended dietary allowance (1996). https://pubmed.ncbi.nlm.nih.gov/8623000/ DOI: 10.1073/pnas.93.8.3704

tissue_or_cell_type

Human circulating neutrophils, monocytes and lymphocytes

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1409–1419

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Seven healthy volunteers hospitalized for 4–6 months in a controlled depletion/repletion study. · source_derived_draft · unverified_draft

### c-leukocyte-concentration-saturation Neutrophils, monocytes and lymphocytes saturated at 100 mg/day and held vitamin C concentrations at least 14 times those in plasma. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Blood cells can concentrate vitamin C; the surrounding plasma does not give the same number. organism: Homo sapiens tissue_or_cell_type: Human circulating neutrophils, monocytes and lymphocytes experimental_model: Seven healthy volunteers hospitalized for 4–6 months in a controlled depletion/repletion study. limitations: Concentration is not an immune-function or infection-prevention endpoint. exposure: Diet below 5 mg vitamin C/day, followed by seven daily doses spanning 30–2500 mg; separate single-dose bioavailability assessments. [c-levine1996] Vitamin C pharmacokinetics in healthy volunteers: evidence for a recommended dietary allowance (1996). https://pubmed.ncbi.nlm.nih.gov/8623000/ DOI: 10.1073/pnas.93.8.3704

experimental_model

LOVIT: multicenter placebo-controlled randomized ICU trial; 872 randomized, 863 in primary analysis, with sepsis and vasopressor use.

exposure

IV vitamin C 50 mg/kg every six hours for up to 96 hours versus matched placebo.

limitations

Confidence interval includes no difference; neither a proven mortality increase alone nor evidence of identical mortality.

nutrient_topic

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

organism

Homo sapiens

plain_language

The combined endpoint and mortality alone had different statistical results.

primary_references

[c-lamontagne2022] Intravenous Vitamin C in Adults with Sepsis in the Intensive Care Unit (2022). https://pubmed.ncbi.nlm.nih.gov/35704292/ DOI: 10.1056/nejmoa2200644

tissue_or_cell_type

Human blood or whole-person endpoints

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1707–1717

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · LOVIT: multicenter placebo-controlled randomized ICU trial; 872 randomized, 863 in primary analysis, with sepsis and vasopressor use. · source_derived_draft · unverified_draft

### c-lovit-mortality-component Day-28 mortality was 35.4% versus 31.6% (RR 1.17, 95% CI 0.98–1.40), while the combined primary endpoint was significant. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: The combined endpoint and mortality alone had different statistical results. organism: Homo sapiens tissue_or_cell_type: Human blood or whole-person endpoints experimental_model: LOVIT: multicenter placebo-controlled randomized ICU trial; 872 randomized, 863 in primary analysis, with sepsis and vasopressor use. limitations: Confidence interval includes no difference; neither a proven mortality increase alone nor evidence of identical mortality. exposure: IV vitamin C 50 mg/kg every six hours for up to 96 hours versus matched placebo. [c-lamontagne2022] Intravenous Vitamin C in Adults with Sepsis in the Intensive Care Unit (2022). https://pubmed.ncbi.nlm.nih.gov/35704292/ DOI: 10.1056/nejmoa2200644

experimental_model

LOVIT: multicenter placebo-controlled randomized ICU trial; 872 randomized, 863 in primary analysis, with sepsis and vasopressor use.

exposure

IV vitamin C 50 mg/kg every six hours for up to 96 hours versus matched placebo.

limitations

The trial did not identify the molecular cause; pharmacologic IV exposure cannot be generalized to food vitamin C or correction of scurvy.

nutrient_topic

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

organism

Homo sapiens

plain_language

In this sepsis population, the tested infusion increased the combined risk of death or ongoing organ-support needs.

primary_references

[c-lamontagne2022] Intravenous Vitamin C in Adults with Sepsis in the Intensive Care Unit (2022). https://pubmed.ncbi.nlm.nih.gov/35704292/ DOI: 10.1056/nejmoa2200644

tissue_or_cell_type

Human blood or whole-person endpoints

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1695–1705

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · LOVIT: multicenter placebo-controlled randomized ICU trial; 872 randomized, 863 in primary analysis, with sepsis and vasopressor use. · source_derived_draft · unverified_draft

### c-lovit-primary-composite The primary composite occurred in 44.5% with IV C versus 38.5% with placebo (RR 1.21, 95% CI 1.04–1.40; P=0.01). Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: In this sepsis population, the tested infusion increased the combined risk of death or ongoing organ-support needs. organism: Homo sapiens tissue_or_cell_type: Human blood or whole-person endpoints experimental_model: LOVIT: multicenter placebo-controlled randomized ICU trial; 872 randomized, 863 in primary analysis, with sepsis and vasopressor use. limitations: The trial did not identify the molecular cause; pharmacologic IV exposure cannot be generalized to food vitamin C or correction of scurvy. exposure: IV vitamin C 50 mg/kg every six hours for up to 96 hours versus matched placebo. [c-lamontagne2022] Intravenous Vitamin C in Adults with Sepsis in the Intensive Care Unit (2022). https://pubmed.ncbi.nlm.nih.gov/35704292/ DOI: 10.1056/nejmoa2200644

experimental_model

Double-blind randomized trial: 100 advanced colorectal cancer patients without previous cytotoxic chemotherapy.

exposure

Oral vitamin C 10 g/day versus placebo. The 1985 abstract does not specify route; route is cross-checked in Chen2005 Introduction, which identifies the two oral randomized trials through references 5 and 6.

limitations

Abstract does not provide the subgroup denominator; no extrapolation to every cancer or pharmacological regimen.

nutrient_topic

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

organism

Homo sapiens

plain_language

The trial did not report a measurable tumor response in that subgroup.

primary_references

[c-moertel1985] High-dose vitamin C versus placebo in the treatment of patients with advanced cancer who have had no prior chemotherapy. A randomized double-blind comparison (1985). https://pubmed.ncbi.nlm.nih.gov/3880867/ DOI: 10.1056/nejm198501173120301

route_provenance

Oral route cross-checked in Chen2005 Introduction and reference 6 (Moertel1985): https://pmc.ncbi.nlm.nih.gov/articles/PMC1224653/ . Clinical outcomes come from the Moertel abstract.

tissue_or_cell_type

Human blood or whole-person endpoints

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1793–1804

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind randomized trial: 100 advanced colorectal cancer patients without previous cytotoxic chemotherapy. · source_derived_draft · unverified_draft

### c-oral-colorectal-objective-response-null No objective improvement occurred among the vitamin C trial participants with measurable disease. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: The trial did not report a measurable tumor response in that subgroup. organism: Homo sapiens tissue_or_cell_type: Human blood or whole-person endpoints experimental_model: Double-blind randomized trial: 100 advanced colorectal cancer patients without previous cytotoxic chemotherapy. limitations: Abstract does not provide the subgroup denominator; no extrapolation to every cancer or pharmacological regimen. exposure: Oral vitamin C 10 g/day versus placebo. The 1985 abstract does not specify route; route is cross-checked in Chen2005 Introduction, which identifies the two oral randomized trials through references 5 and 6. route_provenance: Oral route cross-checked in Chen2005 Introduction and reference 6 (Moertel1985): https://pmc.ncbi.nlm.nih.gov/articles/PMC1224653/ . Clinical outcomes come from the Moertel abstract. [c-moertel1985] High-dose vitamin C versus placebo in the treatment of patients with advanced cancer who have had no prior chemotherapy. A randomized double-blind comparison (1985). https://pubmed.ncbi.nlm.nih.gov/3880867/ DOI: 10.1056/nejm198501173120301

experimental_model

Double-blind randomized trial: 100 advanced colorectal cancer patients without previous cytotoxic chemotherapy.

exposure

Oral vitamin C 10 g/day versus placebo. The 1985 abstract does not specify route; route is cross-checked in Chen2005 Introduction, which identifies the two oral randomized trials through references 5 and 6.

limitations

This historical regimen does not test modern intravenous combination exposures.

nutrient_topic

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

organism

Homo sapiens

plain_language

Time to progression was measured separately from overall survival.

primary_references

[c-moertel1985] High-dose vitamin C versus placebo in the treatment of patients with advanced cancer who have had no prior chemotherapy. A randomized double-blind comparison (1985). https://pubmed.ncbi.nlm.nih.gov/3880867/ DOI: 10.1056/nejm198501173120301

route_provenance

Oral route cross-checked in Chen2005 Introduction and reference 6 (Moertel1985): https://pmc.ncbi.nlm.nih.gov/articles/PMC1224653/ . Clinical outcomes come from the Moertel abstract.

tissue_or_cell_type

Human blood or whole-person endpoints

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1780–1791

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind randomized trial: 100 advanced colorectal cancer patients without previous cytotoxic chemotherapy. · source_derived_draft · unverified_draft

### c-oral-colorectal-progression-null The interval from starting treatment to disease progression did not improve with vitamin C versus placebo. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Time to progression was measured separately from overall survival. organism: Homo sapiens tissue_or_cell_type: Human blood or whole-person endpoints experimental_model: Double-blind randomized trial: 100 advanced colorectal cancer patients without previous cytotoxic chemotherapy. limitations: This historical regimen does not test modern intravenous combination exposures. exposure: Oral vitamin C 10 g/day versus placebo. The 1985 abstract does not specify route; route is cross-checked in Chen2005 Introduction, which identifies the two oral randomized trials through references 5 and 6. route_provenance: Oral route cross-checked in Chen2005 Introduction and reference 6 (Moertel1985): https://pmc.ncbi.nlm.nih.gov/articles/PMC1224653/ . Clinical outcomes come from the Moertel abstract. [c-moertel1985] High-dose vitamin C versus placebo in the treatment of patients with advanced cancer who have had no prior chemotherapy. A randomized double-blind comparison (1985). https://pubmed.ncbi.nlm.nih.gov/3880867/ DOI: 10.1056/nejm198501173120301

experimental_model

Double-blind randomized trial: 100 advanced colorectal cancer patients without previous cytotoxic chemotherapy.

exposure

Oral vitamin C 10 g/day versus placebo. The 1985 abstract does not specify route; route is cross-checked in Chen2005 Introduction, which identifies the two oral randomized trials through references 5 and 6.

limitations

Different cancer, route and cointerventions from modern IV combination trials; not a direct test of their mechanism.

nutrient_topic

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

organism

Homo sapiens

plain_language

The historical randomized trial did not show longer survival for its regimen.

primary_references

[c-moertel1985] High-dose vitamin C versus placebo in the treatment of patients with advanced cancer who have had no prior chemotherapy. A randomized double-blind comparison (1985). https://pubmed.ncbi.nlm.nih.gov/3880867/ DOI: 10.1056/nejm198501173120301

route_provenance

Oral route cross-checked in Chen2005 Introduction and reference 6 (Moertel1985): https://pmc.ncbi.nlm.nih.gov/articles/PMC1224653/ . Clinical outcomes come from the Moertel abstract.

tissue_or_cell_type

Human blood or whole-person endpoints

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1767–1778

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind randomized trial: 100 advanced colorectal cancer patients without previous cytotoxic chemotherapy. · source_derived_draft · unverified_draft

### c-oral-colorectal-survival-null Vitamin C showed no survival advantage over placebo in the advanced colorectal cancer trial. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: The historical randomized trial did not show longer survival for its regimen. organism: Homo sapiens tissue_or_cell_type: Human blood or whole-person endpoints experimental_model: Double-blind randomized trial: 100 advanced colorectal cancer patients without previous cytotoxic chemotherapy. limitations: Different cancer, route and cointerventions from modern IV combination trials; not a direct test of their mechanism. exposure: Oral vitamin C 10 g/day versus placebo. The 1985 abstract does not specify route; route is cross-checked in Chen2005 Introduction, which identifies the two oral randomized trials through references 5 and 6. route_provenance: Oral route cross-checked in Chen2005 Introduction and reference 6 (Moertel1985): https://pmc.ncbi.nlm.nih.gov/articles/PMC1224653/ . Clinical outcomes come from the Moertel abstract. [c-moertel1985] High-dose vitamin C versus placebo in the treatment of patients with advanced cancer who have had no prior chemotherapy. A randomized double-blind comparison (1985). https://pubmed.ncbi.nlm.nih.gov/3880867/ DOI: 10.1056/nejm198501173120301

experimental_model

Seventeen healthy hospitalized volunteers; measured dose/concentration experiments plus pharmacokinetic modeling.

exposure

Measured oral/IV doses 0.015–1.25 g; modeled doses 1–100 g. Larger modeled exposures were not validated in cancer patients.

limitations

Healthy-volunteer pharmacokinetics, not evidence of cancer efficacy.

nutrient_topic

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

organism

Homo sapiens

plain_language

Bypassing the gut produced a much larger blood peak for the same administered amount.

primary_references

[c-padayatty2004] Vitamin C pharmacokinetics: implications for oral and intravenous use (2004). https://pubmed.ncbi.nlm.nih.gov/15068981/ DOI: 10.7326/0003-4819-140-7-200404060-00010

tissue_or_cell_type

Human blood or whole-person endpoints

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1469–1479

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Seventeen healthy hospitalized volunteers; measured dose/concentration experiments plus pharmacokinetic modeling. · source_derived_draft · unverified_draft

### c-oral-iv-measured-peaks At the same measured 1.25-g dose, mean peak plasma vitamin C was 134.8 ± 20.6 micromol/L orally versus 885 ± 201.2 micromol/L intravenously. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Bypassing the gut produced a much larger blood peak for the same administered amount. organism: Homo sapiens tissue_or_cell_type: Human blood or whole-person endpoints experimental_model: Seventeen healthy hospitalized volunteers; measured dose/concentration experiments plus pharmacokinetic modeling. limitations: Healthy-volunteer pharmacokinetics, not evidence of cancer efficacy. exposure: Measured oral/IV doses 0.015–1.25 g; modeled doses 1–100 g. Larger modeled exposures were not validated in cancer patients. [c-padayatty2004] Vitamin C pharmacokinetics: implications for oral and intravenous use (2004). https://pubmed.ncbi.nlm.nih.gov/15068981/ DOI: 10.7326/0003-4819-140-7-200404060-00010

experimental_model

Seventeen healthy hospitalized volunteers; measured dose/concentration experiments plus pharmacokinetic modeling.

exposure

Measured oral/IV doses 0.015–1.25 g; modeled doses 1–100 g. Larger modeled exposures were not validated in cancer patients.

limitations

These high-dose values were calculated, not measured in this study; no patient recommendation or proof of benefit.

nutrient_topic

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

organism

Homo sapiens

plain_language

The model illustrates why oral and intravenous experiments cannot be treated as equivalent exposures.

primary_references

[c-padayatty2004] Vitamin C pharmacokinetics: implications for oral and intravenous use (2004). https://pubmed.ncbi.nlm.nih.gov/15068981/ DOI: 10.7326/0003-4819-140-7-200404060-00010

tissue_or_cell_type

Human blood or whole-person endpoints

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1481–1491

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Seventeen healthy hospitalized volunteers; measured dose/concentration experiments plus pharmacokinetic modeling. · source_derived_draft · unverified_draft

### c-oral-iv-modeled-peaks The model predicted peaks of 220 micromol/L for oral 3 g every four hours and 13400 micromol/L for 50 g IV. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: The model illustrates why oral and intravenous experiments cannot be treated as equivalent exposures. organism: Homo sapiens tissue_or_cell_type: Human blood or whole-person endpoints experimental_model: Seventeen healthy hospitalized volunteers; measured dose/concentration experiments plus pharmacokinetic modeling. limitations: These high-dose values were calculated, not measured in this study; no patient recommendation or proof of benefit. exposure: Measured oral/IV doses 0.015–1.25 g; modeled doses 1–100 g. Larger modeled exposures were not validated in cancer patients. [c-padayatty2004] Vitamin C pharmacokinetics: implications for oral and intravenous use (2004). https://pubmed.ncbi.nlm.nih.gov/15068981/ DOI: 10.7326/0003-4819-140-7-200404060-00010

cross_nutrient

Meal composition modifies the vitamin C/iron interaction.

experimental_model

Human alternate-day paired radiolabeled wheat-roll experiments.

exposure

Seven sodium phytate levels spanning 2–250 mg expressed as phytate phosphorus, with and without ascorbic acid; 55Fe/59Fe labels. Exact C dose and participant count are not extracted from the abstract.

limitations

Single-meal tracer result; does not prove full cancellation of inhibition or long-term correction of anemia.

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 helped offset an iron-absorption inhibitor in the tested meals.

primary_references

[c-hallberg1989] Iron absorption in man: ascorbic acid and dose-dependent inhibition by phytate (1989). https://pubmed.ncbi.nlm.nih.gov/2911999/ DOI: 10.1093/ajcn/49.1.140

tissue_or_cell_type

Human blood or whole-person endpoints

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1580–1591

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human alternate-day paired radiolabeled wheat-roll experiments. · source_derived_draft · unverified_draft

### c-phytate-iron-inhibition-counteraction Added ascorbic acid significantly counteracted the inhibition of radiolabeled nonheme iron absorption caused by sodium phytate in wheat-roll meals. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin C helped offset an iron-absorption inhibitor in the tested meals. organism: Homo sapiens tissue_or_cell_type: Human blood or whole-person endpoints experimental_model: Human alternate-day paired radiolabeled wheat-roll experiments. limitations: Single-meal tracer result; does not prove full cancellation of inhibition or long-term correction of anemia. exposure: Seven sodium phytate levels spanning 2–250 mg expressed as phytate phosphorus, with and without ascorbic acid; 55Fe/59Fe labels. Exact C dose and participant count are not extracted from the abstract. cross_nutrient: Meal composition modifies the vitamin C/iron interaction. [c-hallberg1989] Iron absorption in man: ascorbic acid and dose-dependent inhibition by phytate (1989). https://pubmed.ncbi.nlm.nih.gov/2911999/ DOI: 10.1093/ajcn/49.1.140

experimental_model

Seven healthy volunteers hospitalized for 4–6 months in a controlled depletion/repletion study.

exposure

Diet below 5 mg vitamin C/day, followed by seven daily doses spanning 30–2500 mg; separate single-dose bioavailability assessments.

limitations

Small controlled cohort; saturation is assay- and endpoint-specific. Historical authors’ RDA and safety proposals are not presented as current universal guidance.

nutrient_topic

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

organism

Homo sapiens

plain_language

Taking more changed the blood level much less once the curve flattened.

primary_references

[c-levine1996] Vitamin C pharmacokinetics in healthy volunteers: evidence for a recommended dietary allowance (1996). https://pubmed.ncbi.nlm.nih.gov/8623000/ DOI: 10.1073/pnas.93.8.3704

tissue_or_cell_type

Human blood or whole-person endpoints

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1397–1407

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Seven healthy volunteers hospitalized for 4–6 months in a controlled depletion/repletion study. · source_derived_draft · unverified_draft

### c-plasma-dose-sigmoid Steady-state plasma vitamin C followed a sigmoid dose-response: steepest at 30–100 mg/day, beyond the sigmoid region at 200 mg/day, with complete saturation reported at 1000 mg/day in this cohort. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Taking more changed the blood level much less once the curve flattened. organism: Homo sapiens tissue_or_cell_type: Human blood or whole-person endpoints experimental_model: Seven healthy volunteers hospitalized for 4–6 months in a controlled depletion/repletion study. limitations: Small controlled cohort; saturation is assay- and endpoint-specific. Historical authors’ RDA and safety proposals are not presented as current universal guidance. exposure: Diet below 5 mg vitamin C/day, followed by seven daily doses spanning 30–2500 mg; separate single-dose bioavailability assessments. [c-levine1996] Vitamin C pharmacokinetics in healthy volunteers: evidence for a recommended dietary allowance (1996). https://pubmed.ncbi.nlm.nih.gov/8623000/ DOI: 10.1073/pnas.93.8.3704

experimental_model

Seven healthy volunteers hospitalized for 4–6 months in a controlled depletion/repletion study.

exposure

Diet below 5 mg vitamin C/day, followed by seven daily doses spanning 30–2500 mg; separate single-dose bioavailability assessments.

limitations

Detection limits and individual variation apply; not a universal kidney threshold.

nutrient_topic

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

organism

Homo sapiens

plain_language

The kidney conserved more at low supply and excreted more as supply rose.

primary_references

[c-levine1996] Vitamin C pharmacokinetics in healthy volunteers: evidence for a recommended dietary allowance (1996). https://pubmed.ncbi.nlm.nih.gov/8623000/ DOI: 10.1073/pnas.93.8.3704

tissue_or_cell_type

Human blood or whole-person endpoints

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1433–1443

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Seven healthy volunteers hospitalized for 4–6 months in a controlled depletion/repletion study. · source_derived_draft · unverified_draft

### c-urinary-retention-dose Six of seven volunteers had no detectable urinary vitamin C until the 100-mg dose; higher exposure produced urinary loss. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: The kidney conserved more at low supply and excreted more as supply rose. organism: Homo sapiens tissue_or_cell_type: Human blood or whole-person endpoints experimental_model: Seven healthy volunteers hospitalized for 4–6 months in a controlled depletion/repletion study. limitations: Detection limits and individual variation apply; not a universal kidney threshold. exposure: Diet below 5 mg vitamin C/day, followed by seven daily doses spanning 30–2500 mg; separate single-dose bioavailability assessments. [c-levine1996] Vitamin C pharmacokinetics in healthy volunteers: evidence for a recommended dietary allowance (1996). https://pubmed.ncbi.nlm.nih.gov/8623000/ DOI: 10.1073/pnas.93.8.3704

cross_nutrient

Iron status and dietary matrix affect the observed relationship.

experimental_model

Twelve subjects completing three dietary periods; labeled wheat rolls with every meal for five days per period.

exposure

Self-selected, low-C and high-C complete diets; mean vitamin C intakes spanned 51–247 mg/day.

limitations

Regression within a small dietary experiment is not an isolated randomized causal estimate.

nutrient_topic

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

organism

Homo sapiens

plain_language

The vitamin C association remained visible in an adjusted analysis, even though the period means did not differ significantly.

primary_references

[c-cook2001] Effect of ascorbic acid intake on nonheme-iron absorption from a complete diet (2001). https://pubmed.ncbi.nlm.nih.gov/11124756/ DOI: 10.1093/ajcn/73.1.93

tissue_or_cell_type

Human blood or whole-person endpoints

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1606–1617

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Twelve subjects completing three dietary periods; labeled wheat rolls with every meal for five days per period. · source_derived_draft · unverified_draft

### c-whole-diet-adjusted-iron-association Pooled regression adjusted for iron status found a positive association between ascorbic acid intake and absorption (P=0.0069), alongside associations with animal tissue and phosphate. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: The vitamin C association remained visible in an adjusted analysis, even though the period means did not differ significantly. organism: Homo sapiens tissue_or_cell_type: Human blood or whole-person endpoints experimental_model: Twelve subjects completing three dietary periods; labeled wheat rolls with every meal for five days per period. limitations: Regression within a small dietary experiment is not an isolated randomized causal estimate. exposure: Self-selected, low-C and high-C complete diets; mean vitamin C intakes spanned 51–247 mg/day. cross_nutrient: Iron status and dietary matrix affect the observed relationship. [c-cook2001] Effect of ascorbic acid intake on nonheme-iron absorption from a complete diet (2001). https://pubmed.ncbi.nlm.nih.gov/11124756/ DOI: 10.1093/ajcn/73.1.93

cross_nutrient

Human total-diet boundary on the single-meal interaction.

experimental_model

Twelve subjects completing three dietary periods; labeled wheat rolls with every meal for five days per period.

exposure

Self-selected, low-C and high-C complete diets; mean vitamin C intakes spanned 51–247 mg/day.

limitations

Only twelve participants; meals and iron status also varied. Different design from the phytate challenge, not a draft correction or an unexplained contradiction.

nutrient_topic

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

organism

Homo sapiens

plain_language

An effect visible in a single meal can be much smaller across a complete diet.

primary_references

[c-cook2001] Effect of ascorbic acid intake on nonheme-iron absorption from a complete diet (2001). https://pubmed.ncbi.nlm.nih.gov/11124756/ DOI: 10.1093/ajcn/73.1.93

tissue_or_cell_type

Human blood or whole-person endpoints

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1593–1604

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Twelve subjects completing three dietary periods; labeled wheat rolls with every meal for five days per period. · source_derived_draft · unverified_draft

### c-whole-diet-iron-absorption-null Mean iron absorption did not differ significantly across the three complete-diet periods despite mean vitamin C intakes spanning 51–247 mg/day. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: An effect visible in a single meal can be much smaller across a complete diet. organism: Homo sapiens tissue_or_cell_type: Human blood or whole-person endpoints experimental_model: Twelve subjects completing three dietary periods; labeled wheat rolls with every meal for five days per period. limitations: Only twelve participants; meals and iron status also varied. Different design from the phytate challenge, not a draft correction or an unexplained contradiction. exposure: Self-selected, low-C and high-C complete diets; mean vitamin C intakes spanned 51–247 mg/day. cross_nutrient: Human total-diet boundary on the single-meal interaction. [c-cook2001] Effect of ascorbic acid intake on nonheme-iron absorption from a complete diet (2001). https://pubmed.ncbi.nlm.nih.gov/11124756/ DOI: 10.1093/ajcn/73.1.93

experimental_model

Healthy young women hospitalized for 186 ± 28 days in a depletion/repletion study.

exposure

Vitamin C 30–2500 mg/day at sequential steady states. Participant count is not extracted from the inspected abstract.

limitations

Does not negate ascorbate chemistry or establish no effect on every oxidant, tissue or disease state.

nutrient_topic

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

organism

Homo sapiens

plain_language

Increasing supply did not change these particular oxidative-damage markers in healthy women.

primary_references

[c-levine2001] A new recommended dietary allowance of vitamin C for healthy young women (2001). https://pubmed.ncbi.nlm.nih.gov/11504949/ DOI: 10.1073/pnas.171318198

tissue_or_cell_type

Human blood or whole-person endpoints

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1457–1467

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Healthy young women hospitalized for 186 ± 28 days in a depletion/repletion study. · source_derived_draft · unverified_draft

### c-women-isoprostane-null Plasma and urinary F2-isoprostanes and a major urinary metabolite did not change across the studied vitamin C doses. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Increasing supply did not change these particular oxidative-damage markers in healthy women. organism: Homo sapiens tissue_or_cell_type: Human blood or whole-person endpoints experimental_model: Healthy young women hospitalized for 186 ± 28 days in a depletion/repletion study. limitations: Does not negate ascorbate chemistry or establish no effect on every oxidant, tissue or disease state. exposure: Vitamin C 30–2500 mg/day at sequential steady states. Participant count is not extracted from the inspected abstract. [c-levine2001] A new recommended dietary allowance of vitamin C for healthy young women (2001). https://pubmed.ncbi.nlm.nih.gov/11504949/ DOI: 10.1073/pnas.171318198

experimental_model

Healthy young women hospitalized for 186 ± 28 days in a depletion/repletion study.

exposure

Vitamin C 30–2500 mg/day at sequential steady states. Participant count is not extracted from the inspected abstract.

limitations

Study differences do not establish a fixed sex-specific requirement; these are historical experimental endpoints.

nutrient_topic

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

organism

Homo sapiens

plain_language

The measured pools reached a plateau in this separate cohort.

primary_references

[c-levine2001] A new recommended dietary allowance of vitamin C for healthy young women (2001). https://pubmed.ncbi.nlm.nih.gov/11504949/ DOI: 10.1073/pnas.171318198

tissue_or_cell_type

Human blood or whole-person endpoints

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1445–1455

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Healthy young women hospitalized for 186 ± 28 days in a depletion/repletion study. · source_derived_draft · unverified_draft

### c-women-plasma-saturation In the young-women study, plasma and circulating cells saturated at 400 mg/day, with higher doses eliminated in urine. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: The measured pools reached a plateau in this separate cohort. organism: Homo sapiens tissue_or_cell_type: Human blood or whole-person endpoints experimental_model: Healthy young women hospitalized for 186 ± 28 days in a depletion/repletion study. limitations: Study differences do not establish a fixed sex-specific requirement; these are historical experimental endpoints. exposure: Vitamin C 30–2500 mg/day at sequential steady states. Participant count is not extracted from the inspected abstract. [c-levine2001] A new recommended dietary allowance of vitamin C for healthy young women (2001). https://pubmed.ncbi.nlm.nih.gov/11504949/ DOI: 10.1073/pnas.171318198

experimental_model

CWR22 xenograft model.

limitations

Species, route and exposure matter; this comparison does not justify combining supplements with cancer treatment.

nutrient_topic

EGCG collection; comparator and shared-pathway records retain their actual intervention. · Epigallocatechin-3-gallate (EGCG)

plain_language

Another nutrient comparator did not reproduce high-EGCG antagonism.

primary_references

Preclinical evaluation of the antitumor activity of bortezomib in combination with vitamin C or with epigallocatechin gallate, a component of green tea. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21400028/ · DOI 10.1007/s00280-011-1591-2

EGCG: receptor signaling, metabolism, nutrient interactions and discovery questions (2026-09-18) · lines 444–450

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · CWR22 xenograft model. · source_derived_draft · unverified_draft

## egcg-bortezomib-vitc Another nutrient comparator did not reproduce high-EGCG antagonism. Oral vitamin C at 40 or 500 mg/kg did not antagonize bortezomib in the same mouse experiment. Model: CWR22 xenograft model. Limitations: Species, route and exposure matter; this comparison does not justify combining supplements with cancer treatment. Evidence access: primary abstract. Preclinical evaluation of the antitumor activity of bortezomib in combination with vitamin C or with epigallocatechin gallate, a component of green tea. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21400028/ · DOI 10.1007/s00280-011-1591-2

experimental_model

In-vitro gastric/small-intestinal digestion with HPLC recovery.

limitations

Recovery is chemical survival, not measured human absorption or clinical synergy.

nutrient_topic

EGCG collection; comparator and shared-pathway records retain their actual intervention. · Epigallocatechin-3-gallate (EGCG)

plain_language

Vitamin C protected EGCG in a simulated digestive system.

primary_references

Common tea formulations modulate in vitro digestive recovery of green tea catechins. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17688297/ · DOI 10.1002/mnfr.200700086

EGCG: receptor signaling, metabolism, nutrient interactions and discovery questions (2026-09-18) · lines 452–458

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · In-vitro gastric/small-intestinal digestion with HPLC recovery. · source_derived_draft · unverified_draft

## egcg-vitc-stability Vitamin C protected EGCG in a simulated digestive system. Adding 30 mg ascorbic acid to 250 mL tea increased EGCG recovery after simulated digestion to 54%, versus at most 10% without protective formulation. Model: In-vitro gastric/small-intestinal digestion with HPLC recovery. Limitations: Recovery is chemical survival, not measured human absorption or clinical synergy. Evidence access: primary abstract. Common tea formulations modulate in vitro digestive recovery of green tea catechins. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17688297/ · DOI 10.1002/mnfr.200700086

cross_nutrient

true

evidence_location

Full text lines 29 and 117; Fig. 2E

experimental_model

Antioxidant pretreatment of engineered HEK293/Pank1beta cells

exposure

1 mM vitamin C for 2 hours before 0.5 mM diamide for 30 minutes.

limitations

The endpoint is protein anti-CoA immunoreactivity, not clinical benefit; lower CoAlation is not assumed universally beneficial. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation.

nutrient_topic

Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. · Pantothenate (vitamin B5)

organism

Homo sapiens

plain_language

Vitamin C exposure blunted the measured CoA protein modification during this experimental oxidative challenge.

primary_references

[b5-met-coalation2017] Protein CoAlation: a redox-regulated protein modification by coenzyme A in mammalian cells. (2017). https://pubmed.ncbi.nlm.nih.gov/28341808/ DOI: 10.1042/bcj20170129

tissue_or_cell_type

Engineered HEK293 cultures

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 1075–1087

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Antioxidant pretreatment of engineered HEK293/Pank1beta cells · source_derived_draft · unverified_draft

### b5-met-vitc-coalation Vitamin C pretreatment reduced diamide-induced anti-CoA protein immunoreactivity by approximately 50% in HEK293/Pank1beta cells. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin C exposure blunted the measured CoA protein modification during this experimental oxidative challenge. organism: Homo sapiens tissue_or_cell_type: Engineered HEK293 cultures experimental_model: Antioxidant pretreatment of engineered HEK293/Pank1beta cells limitations: The endpoint is protein anti-CoA immunoreactivity, not clinical benefit; lower CoAlation is not assumed universally beneficial. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation. exposure: 1 mM vitamin C for 2 hours before 0.5 mM diamide for 30 minutes. cross_nutrient: true evidence_location: Full text lines 29 and 117; Fig. 2E [b5-met-coalation2017] Protein CoAlation: a redox-regulated protein modification by coenzyme A in mammalian cells. (2017). https://pubmed.ncbi.nlm.nih.gov/28341808/ DOI: 10.1042/bcj20170129

dose

Tartrazine 700 mg/kg body weight for 2 weeks

duration

2 treatment weeks; endpoint tissue analysis

evidence_access

Primary full-text methods/results and metadata.

evidence_scope

literature_reviewed; source-specific experimental curation

experimental_model

Male Wistar rats; six per group

limitations

Very high animal exposure. Results section reports lower ascorbic acid with no significant GSH or MDA change from tartrazine alone; broader abstract/discussion wording should not replace these results.

nutrient_topic

Tartrazine food-colorant chapter; nutrient, drug and peptide interactions retain their models and limits. · Tartrazine

organism

Male Wistar rats; six per group

plain_language

High-dose oral tartrazine lowered measured brain ascorbic acid in the rat experiment.

primary_references

High-Dose Aspirin Reverses Tartrazine-Induced Cell Growth Dysregulation Independent of p53 Signaling and Antioxidant Mechanisms in Rat Brain. (2019). https://pubmed.ncbi.nlm.nih.gov/31032366/ DOI: 10.1155/2019/9096404

route

Oral tartrazine

tissue

Brain tissue biochemical and histological endpoints

Tartrazine: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 358–367

Original AI-assisted curation of eighteen primary studies. Study-specific citations, negative findings and limitations retained. Not publisher full text. · supports · Male Wistar rats; six per group · source_derived_draft · unverified_draft

## tartrazine-brain-ascorbate High-dose oral tartrazine lowered measured brain ascorbic acid in the rat experiment. Model/species: Male Wistar rats; six per group Tissue: Brain tissue biochemical and histological endpoints Exposure: Tartrazine 700 mg/kg body weight for 2 weeks Route: Oral tartrazine Duration: 2 treatment weeks; endpoint tissue analysis Limits: Very high animal exposure. Results section reports lower ascorbic acid with no significant GSH or MDA change from tartrazine alone; broader abstract/discussion wording should not replace these results. Primary reference: High-Dose Aspirin Reverses Tartrazine-Induced Cell Growth Dysregulation Independent of p53 Signaling and Antioxidant Mechanisms in Rat Brain. (2019). https://pubmed.ncbi.nlm.nih.gov/31032366/ DOI: 10.1155/2019/9096404 Access: Primary full-text methods/results and metadata.

dose

Purified hydroxytyrosol 45 mg/day

duration

8 weeks

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Fourteen human volunteers with mild hyperlipidemia

limitations

The study compared follow-up with baseline and did not resolve the mechanism or prove benefit from combining supplements.

nutrient_topic

Hydroxytyrosol chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Hydroxytyrosol

organism

Fourteen human volunteers with mild hyperlipidemia

plain_language

In 14 volunteers with mild hyperlipidemia, 45 mg/day purified hydroxytyrosol doubled measured vitamin C at weeks 4 and 8 relative to baseline.

primary_references

Hydroxytyrosol supplementation increases vitamin C levels in vivo. A human volunteer trial. (2017). https://pubmed.ncbi.nlm.nih.gov/28063380/ DOI: 10.1016/j.redox.2016.12.014

route

Oral

tissue

Vitamins, minerals and clinical chemistry

Hydroxytyrosol: mechanism of action and interactions (2026-09-20) · lines 99–108

Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · Fourteen human volunteers with mild hyperlipidemia · source_derived_draft · unverified_draft

## hydroxytyrosol-vitamin-c In 14 volunteers with mild hyperlipidemia, 45 mg/day purified hydroxytyrosol doubled measured vitamin C at weeks 4 and 8 relative to baseline. Model/species: Fourteen human volunteers with mild hyperlipidemia Tissue/system: Vitamins, minerals and clinical chemistry Exposure: Purified hydroxytyrosol 45 mg/day Route: Oral Duration: 8 weeks Limits: The study compared follow-up with baseline and did not resolve the mechanism or prove benefit from combining supplements. Primary reference: Hydroxytyrosol supplementation increases vitamin C levels in vivo. A human volunteer trial. (2017). https://pubmed.ncbi.nlm.nih.gov/28063380/ DOI: 10.1016/j.redox.2016.12.014 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

cross_nutrient

true

experimental_model

Physicians Health Study II randomized factorial trial; 14641 male US physicians aged at least 50

exposure

Synthetic alpha-tocopherol 400 IU on alternate days, with factorial vitamin C 500 mg/day; mean follow-up 8 years.

limitations

Mostly primary prevention in male physicians; historical regimen is not nutritional repletion. Primary Methods specify synthetic alpha-tocopherol; no unverified ester identity is attached.

nutrient_topic

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

organism

Homo sapiens

plain_language

The tested vitamin E regimen did not prevent major cardiovascular events in these men.

primary_references

[e-clin-phs2008] Vitamins E and C in the prevention of cardiovascular disease in men: the Physicians' Health Study II randomized controlled trial. (2008). https://pubmed.ncbi.nlm.nih.gov/18997197/ DOI: 10.1001/jama.2008.600

tissue_or_cell_type

Cardiovascular clinical events

Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 1349–1360

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Physicians Health Study II randomized factorial trial; 14641 male US physicians aged at least 50 · source_derived_draft · unverified_draft

### e-clin-phs-cardiovascular Vitamin E did not reduce major cardiovascular events in PHS II (HR 1.01, 95% CI 0.90–1.13). Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: The tested vitamin E regimen did not prevent major cardiovascular events in these men. organism: Homo sapiens tissue_or_cell_type: Cardiovascular clinical events experimental_model: Physicians Health Study II randomized factorial trial; 14641 male US physicians aged at least 50 limitations: Mostly primary prevention in male physicians; historical regimen is not nutritional repletion. Primary Methods specify synthetic alpha-tocopherol; no unverified ester identity is attached. exposure: Synthetic alpha-tocopherol 400 IU on alternate days, with factorial vitamin C 500 mg/day; mean follow-up 8 years. cross_nutrient: true [e-clin-phs2008] Vitamins E and C in the prevention of cardiovascular disease in men: the Physicians' Health Study II randomized controlled trial. (2008). https://pubmed.ncbi.nlm.nih.gov/18997197/ DOI: 10.1001/jama.2008.600