Iron

evidence_span

{"source_cache": "artifacts/copper-research/2912000.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e2d70d43dded75edb026cac237f238d9e59399db6094098796e169f20e819443", "start_char": 0, "end_char": 969, "text_sha256": "e2d70d43dded75edb026cac237f238d9e59399db6094098796e169f20e819443"}

experimental_model

Zinc versus zinc-plus-iron intervention

exposure

50 mg/day zinc with or without 50 mg/day iron for ten weeks

limitations

Study exposures, not dosing recommendations; erythrocyte enzyme activity and ceruloplasmin concentration are distinct endpoints.

nutrient_topic

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

organism

Human adult females

plain_language

Correcting the iron side of an interaction did not correct the copper-related enzyme endpoint.

primary_references

[copper-p2912000] Iron, copper, and zinc status: response to supplementation with zinc or zinc and iron in adult females. (1989). https://pubmed.ncbi.nlm.nih.gov/2912000/ DOI: 10.1093/ajcn/49.1.145

tissue_or_cell_type

Erythrocytes and serum

Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 1170–1181

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Zinc versus zinc-plus-iron intervention · source_derived_draft · unverified_draft

### copper-iron-does-not-prevent-zinc-sod-fall Adding iron to the zinc intervention prevented adverse iron-status changes but did not prevent the fall in erythrocyte Cu/Zn-SOD activity. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Correcting the iron side of an interaction did not correct the copper-related enzyme endpoint. organism: Human adult females tissue_or_cell_type: Erythrocytes and serum experimental_model: Zinc versus zinc-plus-iron intervention limitations: Study exposures, not dosing recommendations; erythrocyte enzyme activity and ceruloplasmin concentration are distinct endpoints. exposure: 50 mg/day zinc with or without 50 mg/day iron for ten weeks evidence_span: {"source_cache": "artifacts/copper-research/2912000.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e2d70d43dded75edb026cac237f238d9e59399db6094098796e169f20e819443", "start_char": 0, "end_char": 969, "text_sha256": "e2d70d43dded75edb026cac237f238d9e59399db6094098796e169f20e819443"} [copper-p2912000] Iron, copper, and zinc status: response to supplementation with zinc or zinc and iron in adult females. (1989). https://pubmed.ncbi.nlm.nih.gov/2912000/ DOI: 10.1093/ajcn/49.1.145

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

The same iron exposure had different effects depending on the starting copper supply.

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 1144–1155

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-lowcu-absorption High dietary iron reduced copper absorption in copper-deficient rats but not in copper-adequate rats in the factorial study. Condition category: nutrient_deficiency nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: The same iron exposure had different effects depending on the starting copper supply. 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

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/chromium-research/29173471.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9de0b60d39b67304da3d1042ebc5f1ed5622a5675e6a0cda4c531bf64249ef2e", "start_char": 0, "end_char": 1448, "text_sha256": "9de0b60d39b67304da3d1042ebc5f1ed5622a5675e6a0cda4c531bf64249ef2e"}

experimental_model

Six-week factorial chromium/iron feeding study

exposure

Iron at 10% versus 100% of the study reference level; chromium propionate at 1, 50 or 500 mg Cr/kg diet

limitations

Very high chromium doses in an animal experiment. Changes do not establish a recommended human ratio, a chromium rescue for anemia or a universal competition rule.

nutrient_topic

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

organism

Female Wistar rats

plain_language

Low iron did not simply free more carrier space and increase chromium accumulation.

primary_references

[chromium-p29173471] The combined effect of supplementary Cr(III) propionate complex and iron deficiency on the chromium and iron status in female rats. (2018). https://pubmed.ncbi.nlm.nih.gov/29173471/ DOI: 10.1016/j.jtemb.2017.10.010

tissue_or_cell_type

Tissue metals and hematologic indices

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Chromium: transport, insulin signaling, nutrient interactions and essentiality debate (2026-09-17) · lines 484–495

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Six-week factorial chromium/iron feeding study · source_derived_draft · unverified_draft

### chromium-iron-deficiency-chromium Chromium supplementation raised tissue chromium less strongly in iron-deficient rats than in rats with adequate iron. Condition category: nutrient_deficiency nutrient_topic: Chromium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Low iron did not simply free more carrier space and increase chromium accumulation. organism: Female Wistar rats tissue_or_cell_type: Tissue metals and hematologic indices experimental_model: Six-week factorial chromium/iron feeding study limitations: Very high chromium doses in an animal experiment. Changes do not establish a recommended human ratio, a chromium rescue for anemia or a universal competition rule. exposure: Iron at 10% versus 100% of the study reference level; chromium propionate at 1, 50 or 500 mg Cr/kg diet evidence_span: {"source_cache": "artifacts/chromium-research/29173471.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9de0b60d39b67304da3d1042ebc5f1ed5622a5675e6a0cda4c531bf64249ef2e", "start_char": 0, "end_char": 1448, "text_sha256": "9de0b60d39b67304da3d1042ebc5f1ed5622a5675e6a0cda4c531bf64249ef2e"} [chromium-p29173471] The combined effect of supplementary Cr(III) propionate complex and iron deficiency on the chromium and iron status in female rats. (2018). https://pubmed.ncbi.nlm.nih.gov/29173471/ DOI: 10.1016/j.jtemb.2017.10.010

evidence_span

{"source_cache": "artifacts/chromium-research/29164513.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4d99145cb86f4110fd0087f9162fa057d87b445b9bc6a60c6467bb310f5e300b", "start_char": 0, "end_char": 2450, "text_sha256": "4d99145cb86f4110fd0087f9162fa057d87b445b9bc6a60c6467bb310f5e300b"}

experimental_model

Factorial six-group iron-excess/chromium feeding experiment

exposure

Iron 45 versus 180 mg/kg diet; chromium propionate 1, 50 or 500 mg Cr/kg diet; six animals/group

limitations

High-dose animal study. The direction changed with background iron; do not extrapolate a universal nutrient antagonism or human dose ratio.

nutrient_topic

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

organism

Female Wistar rats

plain_language

Excess iron changed chromium distribution under these rat feeding conditions.

primary_references

[chromium-p29164513] The Combined Effects of Iron Excess in the Diet and Chromium(III) Supplementation on the Iron and Chromium Status in Female Rats. (2018). https://pubmed.ncbi.nlm.nih.gov/29164513/ DOI: 10.1007/s12011-017-1203-z

tissue_or_cell_type

Serum, liver and kidney metals

Chromium: transport, insulin signaling, nutrient interactions and essentiality debate (2026-09-17) · lines 510–521

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Factorial six-group iron-excess/chromium feeding experiment · source_derived_draft · unverified_draft

### chromium-iron-excess-chromium High dietary iron reduced serum, liver and kidney chromium concentrations in the study. Condition category: normal nutrient_topic: Chromium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Excess iron changed chromium distribution under these rat feeding conditions. organism: Female Wistar rats tissue_or_cell_type: Serum, liver and kidney metals experimental_model: Factorial six-group iron-excess/chromium feeding experiment limitations: High-dose animal study. The direction changed with background iron; do not extrapolate a universal nutrient antagonism or human dose ratio. exposure: Iron 45 versus 180 mg/kg diet; chromium propionate 1, 50 or 500 mg Cr/kg diet; six animals/group evidence_span: {"source_cache": "artifacts/chromium-research/29164513.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4d99145cb86f4110fd0087f9162fa057d87b445b9bc6a60c6467bb310f5e300b", "start_char": 0, "end_char": 2450, "text_sha256": "4d99145cb86f4110fd0087f9162fa057d87b445b9bc6a60c6467bb310f5e300b"} [chromium-p29164513] The Combined Effects of Iron Excess in the Diet and Chromium(III) Supplementation on the Iron and Chromium Status in Female Rats. (2018). https://pubmed.ncbi.nlm.nih.gov/29164513/ DOI: 10.1007/s12011-017-1203-z

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Documented failure of iron response in a specific induced B2-deficiency setting.

experimental_model

Historical induced-depletion study in six men with inoperable cancers; no healthy randomized control group.

exposure

Low-riboflavin semisynthetic diet plus galactoflavin antagonist, followed by riboflavin replacement; three also received oral antibiotics.

limitations

Two cases within a six-person cancer/galactoflavin experiment; cannot generalize this to every anemia or infer a modern treatment regimen.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Homo sapiens

plain_language

More iron did not restore new red-cell production while usable B2 was severely limited in these cases.

primary_references

[b2-lane1964] THE RAPID INDUCTION OF HUMAN RIBOFLAVIN DEFICIENCY WITH GALACTOFLAVIN (1964). https://pubmed.ncbi.nlm.nih.gov/14135487/ DOI: 10.1172/jci104921

tissue_or_cell_type

Circulating reticulocytes

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1814–1825

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Historical induced-depletion study in six men with inoperable cancers; no healthy randomized control group. · source_derived_draft · unverified_draft

### b2-induced-iron-response-failure In two patients with induced B2 deficiency, parenteral iron did not trigger reticulocytosis, whereas subsequent riboflavin did. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: More iron did not restore new red-cell production while usable B2 was severely limited in these cases. organism: Homo sapiens tissue_or_cell_type: Circulating reticulocytes experimental_model: Historical induced-depletion study in six men with inoperable cancers; no healthy randomized control group. limitations: Two cases within a six-person cancer/galactoflavin experiment; cannot generalize this to every anemia or infer a modern treatment regimen. exposure: Low-riboflavin semisynthetic diet plus galactoflavin antagonist, followed by riboflavin replacement; three also received oral antibiotics. cross_nutrient: Documented failure of iron response in a specific induced B2-deficiency setting. [b2-lane1964] THE RAPID INDUCTION OF HUMAN RIBOFLAVIN DEFICIENCY WITH GALACTOFLAVIN (1964). https://pubmed.ncbi.nlm.nih.gov/14135487/ DOI: 10.1172/jci104921

evidence_access

Primary abstract

experimental_model

Purified full-length and truncated human TH1; Mossbauer and X-ray absorption spectroscopy.

limitations

A hydration-dependent structural change is not evidence that ordinary dehydration causes dopamine deficiency.

nutrient_topic

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

plain_language

Iron participates in the enzyme itself, and its local environment matters.

primary_references

Iron coordination geometry in full-length, truncated, and dehydrated forms of human tyrosine hydroxylase studied by Mössbauer and X-ray absorption spectroscopy. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10499095/ · DOI 10.1007/s007750050308

L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 36–42

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified full-length and truncated human TH1; Mossbauer and X-ray absorption spectroscopy. · source_derived_draft · unverified_draft

## l-tyrosine-th-iron Iron participates in the enzyme itself, and its local environment matters. Reconstituted human TH1 contained high-spin Fe(II); dehydration changed iron coordination and rehydration reversed the spectroscopic change. Model: Purified full-length and truncated human TH1; Mossbauer and X-ray absorption spectroscopy. Limitations: A hydration-dependent structural change is not evidence that ordinary dehydration causes dopamine deficiency. Evidence access: Primary abstract Iron coordination geometry in full-length, truncated, and dehydrated forms of human tyrosine hydroxylase studied by Mössbauer and X-ray absorption spectroscopy. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10499095/ · DOI 10.1007/s007750050308

evidence_access

Primary abstract

experimental_model

Human respiratory epithelial-cell exposure to Suwannee River/Nordic reference fulvic fractions; comparison with smoke water-soluble fractions.

limitations

Abstract access; exposure concentration and duration require full-method verification. Increased iron import is consistent with compensatory iron stress, not direct quantification of every intracellular available-iron pool. These are airway-cell exposures, not an oral trial. This is not a recommendation to supplement iron or proof of systemic iron deficiency.

nutrient_topic

Fulvic acid collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Fulvic acid (heterogeneous humic fraction)

plain_language

Adding iron altered the inflammatory response in this experiment.

primary_references

A Fulvic Acid-like Substance Participates in the Pro-inflammatory Effects of Cigarette Smoke and Wood Smoke Particles. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32191033/ · DOI 10.1021/acs.chemrestox.0c00036

Fulvic acid: mixture identity, mineral chemistry, signaling and cross-nutrient mechanisms (2026-09-19) · lines 228–234

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human respiratory epithelial-cell exposure to Suwannee River/Nordic reference fulvic fractions; comparison with smoke water-soluble fractions. · source_derived_draft · unverified_draft

## fulvic-acid-airway-iron-rescue Adding iron altered the inflammatory response in this experiment. Iron co-exposure reduced fulvic-associated IL-6/IL-8 release in the tested cells. Model: Human respiratory epithelial-cell exposure to Suwannee River/Nordic reference fulvic fractions; comparison with smoke water-soluble fractions. Limitations: Abstract access; exposure concentration and duration require full-method verification. Increased iron import is consistent with compensatory iron stress, not direct quantification of every intracellular available-iron pool. These are airway-cell exposures, not an oral trial. This is not a recommendation to supplement iron or proof of systemic iron deficiency. Evidence access: Primary abstract A Fulvic Acid-like Substance Participates in the Pro-inflammatory Effects of Cigarette Smoke and Wood Smoke Particles. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32191033/ · DOI 10.1021/acs.chemrestox.0c00036

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

true

evidence_location

Primary indexed abstract.

experimental_model

Nine-month randomized double-blind controlled trial in 377 goitrous children aged 6–15 with high anemia prevalence

exposure

Iodized salt 25 micrograms iodine/g versus dual-fortified salt with the same iodine plus 1 mg iron/g as microencapsulated ferrous sulfate; 40-week measurements.

limitations

Clinical intervention and thyroid endpoints do not identify the exact iron-dependent step. Iodized-salt-only participants also improved. Related publications from this cohort are not independent trials. The abstract does not provide the exact between-group thyroxine effect size. The two iron trials have distinct populations and endpoints; their hormone results are not declared a contradiction.

nutrient_topic

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

organism

Homo sapiens

plain_language

This iron–iodine trial also found a hormone response.

primary_references

[iod-clin-zimmer2002] Addition of microencapsulated iron to iodized salt improves the efficacy of iodine in goitrous, iron-deficient children: a randomized, double-blind, controlled trial. (2002). https://pubmed.ncbi.nlm.nih.gov/12457449/ DOI: 10.1530/eje.0.1470747

tissue_or_cell_type

Thyroid volume, circulating thyroxine and iron indices

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 1244–1256

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Nine-month randomized double-blind controlled trial in 377 goitrous children aged 6–15 with high anemia prevalence · source_derived_draft · unverified_draft

### iod-clin-dual-salt-thyroxine Serum thyroxine was higher with dual-fortified salt than with iodized salt alone (P<0.05), with lower reported hypothyroidism and goiter prevalence (P<0.01). Condition category: nutrient_deficiency nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: This iron–iodine trial also found a hormone response. organism: Homo sapiens tissue_or_cell_type: Thyroid volume, circulating thyroxine and iron indices experimental_model: Nine-month randomized double-blind controlled trial in 377 goitrous children aged 6–15 with high anemia prevalence limitations: Clinical intervention and thyroid endpoints do not identify the exact iron-dependent step. Iodized-salt-only participants also improved. Related publications from this cohort are not independent trials. The abstract does not provide the exact between-group thyroxine effect size. The two iron trials have distinct populations and endpoints; their hormone results are not declared a contradiction. exposure: Iodized salt 25 micrograms iodine/g versus dual-fortified salt with the same iodine plus 1 mg iron/g as microencapsulated ferrous sulfate; 40-week measurements. cross_nutrient: true evidence_location: Primary indexed abstract. [iod-clin-zimmer2002] Addition of microencapsulated iron to iodized salt improves the efficacy of iodine in goitrous, iron-deficient children: a randomized, double-blind, controlled trial. (2002). https://pubmed.ncbi.nlm.nih.gov/12457449/ DOI: 10.1530/eje.0.1470747

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

true

evidence_location

Primary indexed abstract.

experimental_model

Nine-month randomized double-blind controlled trial in 377 goitrous children aged 6–15 with high anemia prevalence

exposure

Iodized salt 25 micrograms iodine/g versus dual-fortified salt with the same iodine plus 1 mg iron/g as microencapsulated ferrous sulfate; 40-week measurements.

limitations

Clinical intervention and thyroid endpoints do not identify the exact iron-dependent step. Iodized-salt-only participants also improved. Related publications from this cohort are not independent trials.

nutrient_topic

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

organism

Homo sapiens

plain_language

Adding iron improved the response to the same amount of iodine in this trial.

primary_references

[iod-clin-zimmer2002] Addition of microencapsulated iron to iodized salt improves the efficacy of iodine in goitrous, iron-deficient children: a randomized, double-blind, controlled trial. (2002). https://pubmed.ncbi.nlm.nih.gov/12457449/ DOI: 10.1530/eje.0.1470747

tissue_or_cell_type

Thyroid volume, circulating thyroxine and iron indices

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 1230–1242

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Nine-month randomized double-blind controlled trial in 377 goitrous children aged 6–15 with high anemia prevalence · source_derived_draft · unverified_draft

### iod-clin-dual-salt-volume Mean thyroid-volume reduction at 40 weeks was 38% with dual iron–iodine salt versus 18% with iodine-only salt (P<0.01). Condition category: nutrient_deficiency nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Adding iron improved the response to the same amount of iodine in this trial. organism: Homo sapiens tissue_or_cell_type: Thyroid volume, circulating thyroxine and iron indices experimental_model: Nine-month randomized double-blind controlled trial in 377 goitrous children aged 6–15 with high anemia prevalence limitations: Clinical intervention and thyroid endpoints do not identify the exact iron-dependent step. Iodized-salt-only participants also improved. Related publications from this cohort are not independent trials. exposure: Iodized salt 25 micrograms iodine/g versus dual-fortified salt with the same iodine plus 1 mg iron/g as microencapsulated ferrous sulfate; 40-week measurements. cross_nutrient: true evidence_location: Primary indexed abstract. [iod-clin-zimmer2002] Addition of microencapsulated iron to iodized salt improves the efficacy of iodine in goitrous, iron-deficient children: a randomized, double-blind, controlled trial. (2002). https://pubmed.ncbi.nlm.nih.gov/12457449/ DOI: 10.1530/eje.0.1470747

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

true

evidence_location

Primary indexed abstract.

experimental_model

Randomized double-blind placebo-controlled trial in 166 goitrous iron-deficient children aged 5–14 in Côte d’Ivoire

exposure

All consumed iodized salt providing 10–30 mg iodine/kg salt at household level; iron group received 60 mg elemental Fe/day, four days/week for 16 weeks; outcomes followed to 20 weeks.

limitations

This tests iron treatment on a background of iodine supply. It does not directly measure TPO activity or prove that iron deficiency always prevents iodine response. Specific iron-supplement salt not verified from abstract. The whole-blood thyrotropin assay is identified explicitly; it is not claimed to be the same specimen matrix as serum TSH.

nutrient_topic

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

organism

Homo sapiens

plain_language

Improved thyroid size did not mean every hormone measurement changed.

primary_references

[iod-clin-hess2002] Treatment of iron deficiency in goitrous children improves the efficacy of iodized salt in Côte d'Ivoire. (2002). https://pubmed.ncbi.nlm.nih.gov/11916762/ DOI: 10.1093/ajcn/75.4.743

tissue_or_cell_type

Thyroid ultrasound and blood thyroid indices

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 1216–1228

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized double-blind placebo-controlled trial in 166 goitrous iron-deficient children aged 5–14 in Côte d’Ivoire · source_derived_draft · unverified_draft

### iod-clin-iron-salt-hormone-null The iron and placebo groups showed no significant difference in serum thyroxine or whole-blood thyrotropin at baseline or during the intervention. Condition category: nutrient_deficiency nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Improved thyroid size did not mean every hormone measurement changed. organism: Homo sapiens tissue_or_cell_type: Thyroid ultrasound and blood thyroid indices experimental_model: Randomized double-blind placebo-controlled trial in 166 goitrous iron-deficient children aged 5–14 in Côte d’Ivoire limitations: This tests iron treatment on a background of iodine supply. It does not directly measure TPO activity or prove that iron deficiency always prevents iodine response. Specific iron-supplement salt not verified from abstract. The whole-blood thyrotropin assay is identified explicitly; it is not claimed to be the same specimen matrix as serum TSH. exposure: All consumed iodized salt providing 10–30 mg iodine/kg salt at household level; iron group received 60 mg elemental Fe/day, four days/week for 16 weeks; outcomes followed to 20 weeks. cross_nutrient: true evidence_location: Primary indexed abstract. [iod-clin-hess2002] Treatment of iron deficiency in goitrous children improves the efficacy of iodized salt in Côte d'Ivoire. (2002). https://pubmed.ncbi.nlm.nih.gov/11916762/ DOI: 10.1093/ajcn/75.4.743

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

true

evidence_location

Primary indexed abstract.

experimental_model

Randomized double-blind placebo-controlled trial in 166 goitrous iron-deficient children aged 5–14 in Côte d’Ivoire

exposure

All consumed iodized salt providing 10–30 mg iodine/kg salt at household level; iron group received 60 mg elemental Fe/day, four days/week for 16 weeks; outcomes followed to 20 weeks.

limitations

This tests iron treatment on a background of iodine supply. It does not directly measure TPO activity or prove that iron deficiency always prevents iodine response. Specific iron-supplement salt not verified from abstract.

nutrient_topic

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

organism

Homo sapiens

plain_language

Correcting iron deficiency improved the thyroid-size response while iodine was supplied.

primary_references

[iod-clin-hess2002] Treatment of iron deficiency in goitrous children improves the efficacy of iodized salt in Côte d'Ivoire. (2002). https://pubmed.ncbi.nlm.nih.gov/11916762/ DOI: 10.1093/ajcn/75.4.743

tissue_or_cell_type

Thyroid ultrasound and blood thyroid indices

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 1202–1214

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized double-blind placebo-controlled trial in 166 goitrous iron-deficient children aged 5–14 in Côte d’Ivoire · source_derived_draft · unverified_draft

### iod-clin-iron-salt-volume At 20 weeks, thyroid volume fell 22.8 ± 10.7% with iron treatment versus 12.7 ± 10.1% with placebo in children already using iodized salt (P<0.01). Condition category: nutrient_deficiency nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Correcting iron deficiency improved the thyroid-size response while iodine was supplied. organism: Homo sapiens tissue_or_cell_type: Thyroid ultrasound and blood thyroid indices experimental_model: Randomized double-blind placebo-controlled trial in 166 goitrous iron-deficient children aged 5–14 in Côte d’Ivoire limitations: This tests iron treatment on a background of iodine supply. It does not directly measure TPO activity or prove that iron deficiency always prevents iodine response. Specific iron-supplement salt not verified from abstract. exposure: All consumed iodized salt providing 10–30 mg iodine/kg salt at household level; iron group received 60 mg elemental Fe/day, four days/week for 16 weeks; outcomes followed to 20 weeks. cross_nutrient: true evidence_location: Primary indexed abstract. [iod-clin-hess2002] Treatment of iron deficiency in goitrous children improves the efficacy of iodized salt in Côte d'Ivoire. (2002). https://pubmed.ncbi.nlm.nih.gov/11916762/ DOI: 10.1093/ajcn/75.4.743

evidence_span

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experimental_model

Crystal structure of rat tyrosine hydroxylase with a cofactor analogue and iron at 2.3 angstrom

exposure

Bound 7,8-dihydrobiopterin and iron

limitations

Structural chemistry of the rate-limiting step. It is a rat enzyme structure with a cofactor analogue, not a measurement of iron status in an animal.

nutrient_topic

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

organism

Rat enzyme

plain_language

The first and slowest step of making noradrenaline needs an iron atom and a molecule of oxygen.

primary_references

[cold-p9753429] Crystal structure of tyrosine hydroxylase with bound cofactor analogue and iron at 2.3 A resolution: self-hydroxylation of Phe300 and the pterin-binding site. (1998). https://pubmed.ncbi.nlm.nih.gov/9753429/ DOI: 10.1021/bi981462g

tissue_or_cell_type

Purified catalytic and tetramerization domains

Cold water immersion: cold sensing, heat production, the catecholamine axis and what repeated exposure changes (2026-09-19) · lines 533–544

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Crystal structure of rat tyrosine hydroxylase with a cofactor analogue and iron at 2.3 angstrom · source_derived_draft · unverified_draft

### cold-th-iron-oxygen-pterin Tyrosine hydroxylase is a non-heme iron enzyme that uses molecular oxygen to hydroxylate tyrosine to L-DOPA and tetrahydrobiopterin to 4a-hydroxybiopterin in the rate-limiting step of the catecholamine biosynthetic pathway. Condition category: normal nutrient_topic: Cold water immersion research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: The first and slowest step of making noradrenaline needs an iron atom and a molecule of oxygen. organism: Rat enzyme tissue_or_cell_type: Purified catalytic and tetramerization domains experimental_model: Crystal structure of rat tyrosine hydroxylase with a cofactor analogue and iron at 2.3 angstrom limitations: Structural chemistry of the rate-limiting step. It is a rat enzyme structure with a cofactor analogue, not a measurement of iron status in an animal. exposure: Bound 7,8-dihydrobiopterin and iron evidence_span: {"source_cache": "artifacts/cold-research/9753429.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3c76ec6d5dadb463c0a044175d5a78fbd02df4da7c339029c8c232e8878175b9", "start_char": 0, "end_char": 1695, "text_sha256": "3c76ec6d5dadb463c0a044175d5a78fbd02df4da7c339029c8c232e8878175b9"} [cold-p9753429] Crystal structure of tyrosine hydroxylase with bound cofactor analogue and iron at 2.3 A resolution: self-hydroxylation of Phe300 and the pterin-binding site. (1998). https://pubmed.ncbi.nlm.nih.gov/9753429/ DOI: 10.1021/bi981462g

cross_nutrient

Manganese (measured_nutrient)

evidence_span

{"source_cache": "artifacts/manganese-clinical-sources/davidsson1991.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "7570e2285532eac2292b252a3813f1be97b46d68529a4d4150a88b4f9038676a", "start_char": 0, "end_char": 912, "text_sha256": "7570e2285532eac2292b252a3813f1be97b46d68529a4d4150a88b4f9038676a", "text_characters": 912}

experimental_model

Paired radiotracer test-meal study in adults

exposure

Human milk, infant formula and wheat bread used as adult test meals; individual mineral and dietary-component additions.

limitations

These were adult experiments even when milk or infant formula was the matrix. Added amounts were not independently verified from the indexed abstract; no universal interaction or spacing rule follows.

nutrient_topic

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

organism

Homo sapiens

plain_language

An iron interaction was not detected in every meal.

primary_references

[mn-clin-davidsson1991] The effect of individual dietary components on manganese absorption in humans. (1991). https://pubmed.ncbi.nlm.nih.gov/1957822/ DOI: 10.1093/ajcn/54.6.1065

tissue_or_cell_type

Intestinal absorption

Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 1034–1046

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Paired radiotracer test-meal study in adults · source_derived_draft · unverified_draft

### mn-clin-meal-iron Iron added to the wheat-bread test meal did not significantly change manganese absorption. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: An iron interaction was not detected in every meal. organism: Homo sapiens tissue_or_cell_type: Intestinal absorption experimental_model: Paired radiotracer test-meal study in adults limitations: These were adult experiments even when milk or infant formula was the matrix. Added amounts were not independently verified from the indexed abstract; no universal interaction or spacing rule follows. exposure: Human milk, infant formula and wheat bread used as adult test meals; individual mineral and dietary-component additions. cross_nutrient: Manganese (measured_nutrient) evidence_span: {"source_cache": "artifacts/manganese-clinical-sources/davidsson1991.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "7570e2285532eac2292b252a3813f1be97b46d68529a4d4150a88b4f9038676a", "start_char": 0, "end_char": 912, "text_sha256": "7570e2285532eac2292b252a3813f1be97b46d68529a4d4150a88b4f9038676a", "text_characters": 912} [mn-clin-davidsson1991] The effect of individual dietary components on manganese absorption in humans. (1991). https://pubmed.ncbi.nlm.nih.gov/1957822/ DOI: 10.1093/ajcn/54.6.1065

cross_nutrient

Iron excess altered occupancy of a Mn enzyme.

experimental_model

Purified SOD2, SOD2-overexpressing human cells, and dietary C57BL/6J mouse experiments

exposure

Five-week-old male C57BL/6J mice; 2700 ppm Fe and 150 ppm Mn versus control 275 ppm Fe and 150 ppm Mn, four weeks.

limitations

Experimental iron excess, not iron deficiency or a human oral-dose equivalence.

nutrient_topic

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

organism

Mus musculus

plain_language

A high-iron mouse diet shifted Sod2 toward iron loading.

primary_references

[mn-enz-29398562] Switch of Mitochondrial Superoxide Dismutase into a Prooxidant Peroxidase in Manganese-Deficient Cells and Mice. (2018). https://pubmed.ncbi.nlm.nih.gov/29398562/ DOI: 10.1016/j.chembiol.2018.01.007

tissue_or_cell_type

Liver Sod2

Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 521–532

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified SOD2, SOD2-overexpressing human cells, and dietary C57BL/6J mouse experiments · source_derived_draft · unverified_draft

### mn-enz-mouse-high-fe-iron-sod2 After four weeks on the iron-enriched diet, nearly 80% of isolated mouse liver Sod2 was iron-loaded. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: A high-iron mouse diet shifted Sod2 toward iron loading. organism: Mus musculus tissue_or_cell_type: Liver Sod2 experimental_model: Purified SOD2, SOD2-overexpressing human cells, and dietary C57BL/6J mouse experiments limitations: Experimental iron excess, not iron deficiency or a human oral-dose equivalence. exposure: Five-week-old male C57BL/6J mice; 2700 ppm Fe and 150 ppm Mn versus control 275 ppm Fe and 150 ppm Mn, four weeks. cross_nutrient: Iron excess altered occupancy of a Mn enzyme. [mn-enz-29398562] Switch of Mitochondrial Superoxide Dismutase into a Prooxidant Peroxidase in Manganese-Deficient Cells and Mice. (2018). https://pubmed.ncbi.nlm.nih.gov/29398562/ DOI: 10.1016/j.chembiol.2018.01.007

cross_nutrient

Iron/zinc -> retinoid transport markers.

experimental_model

Same factorial trial.

limitations

Measured biomarkers do not prove the molecular mechanism.

nutrient_topic

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

organism

Homo sapiens

plain_language

The two minerals did not produce identical carrier-protein responses.

primary_references

[va-munoz2000] Iron and zinc supplementation improves indicators of vitamin A status of Mexican preschoolers (2000). https://pubmed.ncbi.nlm.nih.gov/10702174/ DOI: 10.1093/ajcn/71.3.789

tissue_or_cell_type

Plasma

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1495–1505

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Same factorial trial. · source_derived_draft · unverified_draft

### va-iron-improves-retinol-marker Iron increased plasma retinol, RBP and transthyretin; the combined iron/zinc arm increased retinol without significant carrier-protein increases. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: The two minerals did not produce identical carrier-protein responses. organism: Homo sapiens tissue_or_cell_type: Plasma experimental_model: Same factorial trial. limitations: Measured biomarkers do not prove the molecular mechanism. cross_nutrient: Iron/zinc -> retinoid transport markers. [va-munoz2000] Iron and zinc supplementation improves indicators of vitamin A status of Mexican preschoolers (2000). https://pubmed.ncbi.nlm.nih.gov/10702174/ DOI: 10.1093/ajcn/71.3.789

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

Direct cellular iron-to-vitamin-A precursor interaction.

evidence_location

Abstract

experimental_model

Human small-intestinal mucosa and Caco-2 TC7 cells; desferrioxamine and iron addition.

exposure

Iron added during the chelation experiment.

limitations

Accessible source does not resolve the added salt/speciation; not a clinical repletion result.

nutrient_topic

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

organism

Homo sapiens

outcome

Adding iron reversed desferrioxamine inhibition of carotenoid cleavage in TC7 cells.

plain_language

Iron restored the inhibited retinal-producing reaction.

primary_references

[va-during-2001] beta-Carotene 15,15'-Dioxygenase activity in human tissues and cells: evidence of an iron dependency (2001). https://pubmed.ncbi.nlm.nih.gov/12031257/ DOI: 10.1016/S0955-2863(01)00184-X

tissue_or_cell_type

Caco-2 TC7 cells

trigger_kind

machinery_impairment Imported condition classification; unverified.

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 202–215

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human small-intestinal mucosa and Caco-2 TC7 cells; desferrioxamine and iron addition. · source_derived_draft · unverified_draft

### va-iron-rescue-cleavage Adding iron reversed desferrioxamine inhibition of carotenoid cleavage in TC7 cells. Condition category: machinery_impairment nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Iron restored the inhibited retinal-producing reaction. organism: Homo sapiens tissue_or_cell_type: Caco-2 TC7 cells experimental_model: Human small-intestinal mucosa and Caco-2 TC7 cells; desferrioxamine and iron addition. limitations: Accessible source does not resolve the added salt/speciation; not a clinical repletion result. exposure: Iron added during the chelation experiment. outcome: Adding iron reversed desferrioxamine inhibition of carotenoid cleavage in TC7 cells. evidence_location: Abstract cross_nutrient: Direct cellular iron-to-vitamin-A precursor interaction. [va-during-2001] beta-Carotene 15,15'-Dioxygenase activity in human tissues and cells: evidence of an iron dependency (2001). https://pubmed.ncbi.nlm.nih.gov/12031257/ DOI: 10.1016/S0955-2863(01)00184-X

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_span

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experimental_model

Protein association, ubiquitination and degradation experiments

exposure

Iron and oxygen availability; FBXL5 stability

limitations

Cellular sensing mechanism, not a serum-iron diagnostic rule.

nutrient_topic

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

organism

Mammalian cellular systems

plain_language

The control system responds to both iron and oxygen availability.

primary_references

[iron-p19762596] Control of iron homeostasis by an iron-regulated ubiquitin ligase. (2009). https://pubmed.ncbi.nlm.nih.gov/19762596/ DOI: 10.1126/science.1176333

tissue_or_cell_type

Cytosolic iron regulation

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 693–704

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Protein association, ubiquitination and degradation experiments · source_derived_draft · unverified_draft

### iron-fbxl5-iron-sensing Iron or oxygen depletion triggered FBXL5 degradation through a process requiring its N-terminal hemerythrin-like iron-binding domain. Condition category: nutrient_deficiency nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: The control system responds to both iron and oxygen availability. organism: Mammalian cellular systems tissue_or_cell_type: Cytosolic iron regulation experimental_model: Protein association, ubiquitination and degradation experiments limitations: Cellular sensing mechanism, not a serum-iron diagnostic rule. exposure: Iron and oxygen availability; FBXL5 stability evidence_span: {"source_cache": "artifacts/iron-research/19762596.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9308ac435b303ee150d6c92a21c3d68731fed61f0894312026a8a19e57d5aac6", "start_char": 0, "end_char": 824, "text_sha256": "9308ac435b303ee150d6c92a21c3d68731fed61f0894312026a8a19e57d5aac6"} [iron-p19762596] Control of iron homeostasis by an iron-regulated ubiquitin ligase. (2009). https://pubmed.ncbi.nlm.nih.gov/19762596/ DOI: 10.1126/science.1176333

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/iron-research/27537180.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "59f2a83f1bffcacfed0df109f3690413aa2e6f08be6ad400817c5cbe2165e523", "start_char": 0, "end_char": 1840, "text_sha256": "59f2a83f1bffcacfed0df109f3690413aa2e6f08be6ad400817c5cbe2165e523"}

experimental_model

Five-week factorial iron/copper feeding

exposure

Approximately 8800, 80 or 11 ppm iron crossed with approximately 183, 8 or 0.9 ppm copper

limitations

Very high experimental iron exposure; not an estimate of human supplement risk at ordinary intake. Copper restoration did not normalize every iron measure.

nutrient_topic

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

organism

Weanling male Sprague-Dawley rats

plain_language

Anemia developed despite abundant iron because another part of iron handling became deficient.

primary_references

[iron-p27537180] High-Iron Consumption Impairs Growth and Causes Copper-Deficiency Anemia in Weanling Sprague-Dawley Rats. (2016). https://pubmed.ncbi.nlm.nih.gov/27537180/ DOI: 10.1371/journal.pone.0161033

tissue_or_cell_type

Systemic copper and iron status

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 914–925

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Five-week factorial iron/copper feeding · source_derived_draft · unverified_draft

### iron-high-iron-copper-deficiency Very-high-iron feeding caused low serum/tissue copper, reduced circulating ceruloplasmin activity, anemia and cardiac hypertrophy in the studied rats. Condition category: nutrient_deficiency nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: Anemia developed despite abundant iron because another part of iron handling became deficient. organism: Weanling male Sprague-Dawley rats tissue_or_cell_type: Systemic copper and iron status experimental_model: Five-week factorial iron/copper feeding limitations: Very high experimental iron exposure; not an estimate of human supplement risk at ordinary intake. Copper restoration did not normalize every iron measure. exposure: Approximately 8800, 80 or 11 ppm iron crossed with approximately 183, 8 or 0.9 ppm copper evidence_span: {"source_cache": "artifacts/iron-research/27537180.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "59f2a83f1bffcacfed0df109f3690413aa2e6f08be6ad400817c5cbe2165e523", "start_char": 0, "end_char": 1840, "text_sha256": "59f2a83f1bffcacfed0df109f3690413aa2e6f08be6ad400817c5cbe2165e523"} [iron-p27537180] High-Iron Consumption Impairs Growth and Causes Copper-Deficiency Anemia in Weanling Sprague-Dawley Rats. (2016). https://pubmed.ncbi.nlm.nih.gov/27537180/ DOI: 10.1371/journal.pone.0161033

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/iron-research/12097675.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "26b7a5ddb0985abdb2325c7ecd505c46f02604bd4d35f68ed0c9ad67113a148e", "start_char": 0, "end_char": 1527, "text_sha256": "26b7a5ddb0985abdb2325c7ecd505c46f02604bd4d35f68ed0c9ad67113a148e"}

experimental_model

Controlled iron-deficient diets with pair-fed controls

exposure

Four weeks of graded iron restriction; separate food-restriction controls

limitations

Food restriction also reduced TPO; the iron effect was separately estimated. No human serum threshold or automatic iodine-treatment failure rule.

nutrient_topic

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

organism

84 male weanling rats

plain_language

Iodine supply is only part of thyroid-hormone synthesis; its working enzyme also depends on iron-containing heme.

primary_references

[iron-p12097675] Iron deficiency anemia reduces thyroid peroxidase activity in rats. (2002). https://pubmed.ncbi.nlm.nih.gov/12097675/ DOI: 10.1093/jn/132.7.1951

tissue_or_cell_type

Thyroid and blood

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 901–912

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Controlled iron-deficient diets with pair-fed controls · source_derived_draft · unverified_draft

### iron-iron-tpo-deficiency Iron-deficiency anemia independently reduced thyroid peroxidase activity after accounting for food restriction in the rat experiment. Condition category: nutrient_deficiency nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: Iodine supply is only part of thyroid-hormone synthesis; its working enzyme also depends on iron-containing heme. organism: 84 male weanling rats tissue_or_cell_type: Thyroid and blood experimental_model: Controlled iron-deficient diets with pair-fed controls limitations: Food restriction also reduced TPO; the iron effect was separately estimated. No human serum threshold or automatic iodine-treatment failure rule. exposure: Four weeks of graded iron restriction; separate food-restriction controls evidence_span: {"source_cache": "artifacts/iron-research/12097675.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "26b7a5ddb0985abdb2325c7ecd505c46f02604bd4d35f68ed0c9ad67113a148e", "start_char": 0, "end_char": 1527, "text_sha256": "26b7a5ddb0985abdb2325c7ecd505c46f02604bd4d35f68ed0c9ad67113a148e"} [iron-p12097675] Iron deficiency anemia reduces thyroid peroxidase activity in rats. (2002). https://pubmed.ncbi.nlm.nih.gov/12097675/ DOI: 10.1093/jn/132.7.1951

cross_nutrient

Drug-modified B6 chemistry creates an iron-binding molecule.

experimental_model

Cell-free chemistry, primary human hepatocytes and HepG2/C3A cells

exposure

Chrome azurol S assay; biochemical and cell-medium samples.

limitations

This endpoint does not establish nutritional iron deficiency in patients.

nutrient_topic

Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6

organism

Not applicable; chemical reaction

plain_language

The drug-B6 product also interacts with iron.

primary_references

[brewer-2019-isoniazid] The Isoniazid Metabolites Hydrazine and Pyridoxal Isonicotinoyl Hydrazone Modulate Heme Biosynthesis (2019). https://pmc.ncbi.nlm.nih.gov/articles/PMC6390808/ DOI: 10.1093/toxsci/kfy294

tissue_or_cell_type

Cell-free chelation assay

Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1283–1294

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell-free chemistry, primary human hepatocytes and HepG2/C3A cells · source_derived_draft · unverified_draft

### b6-neuro-pih-iron-chelation The B6-isoniazid conjugate PIH bound iron in the study chelation assay. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The drug-B6 product also interacts with iron. organism: Not applicable; chemical reaction tissue_or_cell_type: Cell-free chelation assay experimental_model: Cell-free chemistry, primary human hepatocytes and HepG2/C3A cells limitations: This endpoint does not establish nutritional iron deficiency in patients. exposure: Chrome azurol S assay; biochemical and cell-medium samples. cross_nutrient: Drug-modified B6 chemistry creates an iron-binding molecule. [brewer-2019-isoniazid] The Isoniazid Metabolites Hydrazine and Pyridoxal Isonicotinoyl Hydrazone Modulate Heme Biosynthesis (2019). https://pmc.ncbi.nlm.nih.gov/articles/PMC6390808/ DOI: 10.1093/toxsci/kfy294

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Thiamine disruption accompanies altered local iron handling; iron intake, chelation and iron-repletion response were not tested.

evidence_location

Results: Ferritin, Iron, and Microglial Responses to TD; Figure 7

evidence_span

iron accumulated in microglia

experimental_model

Adult male C57BL/6 mice and Fischer 344 Brown Norway F1 rats; thiamine-deficient diet plus pyrithiamine 0.5 mg/kg/day intraperitoneally; staged brain histochemistry.

exposure

Dietary thiamine removal plus daily pyrithiamine in mice or rats

limitations

Histochemistry does not establish iron origin, oxidation state or that dietary iron caused injury.

nutrient_topic

Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)

organism

Mus musculus; Rattus norvegicus

plain_language

Severe depletion changed where iron was retained in the brain.

primary_references

[calingasan-1998-bbb-iron-nos] Induction of nitric oxide synthase and microglial responses precede selective cell death induced by chronic impairment of oxidative metabolism (1998). https://pmc.ncbi.nlm.nih.gov/articles/PMC1852979/ DOI: 10.1016/S0002-9440(10)65602-7

tissue_or_cell_type

Microglia in vulnerable thalamic and geniculate regions; rat inferior colliculus

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1225–1238

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Adult male C57BL/6 mice and Fischer 344 Brown Norway F1 rats; thiamine-deficient diet plus pyrithiamine 0.5 mg/kg/day intraperitoneally; staged brain histochemistry. · source_derived_draft · unverified_draft

### thiamine-def-microglial-iron-accumulation Iron accumulated in microglia of vulnerable mouse regions from day 10; rat iron-laden microglia often clustered near vessels. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Severe depletion changed where iron was retained in the brain. organism: Mus musculus; Rattus norvegicus tissue_or_cell_type: Microglia in vulnerable thalamic and geniculate regions; rat inferior colliculus experimental_model: Adult male C57BL/6 mice and Fischer 344 Brown Norway F1 rats; thiamine-deficient diet plus pyrithiamine 0.5 mg/kg/day intraperitoneally; staged brain histochemistry. limitations: Histochemistry does not establish iron origin, oxidation state or that dietary iron caused injury. evidence_location: Results: Ferritin, Iron, and Microglial Responses to TD; Figure 7 evidence_span: iron accumulated in microglia cross_nutrient: Thiamine disruption accompanies altered local iron handling; iron intake, chelation and iron-repletion response were not tested. exposure: Dietary thiamine removal plus daily pyrithiamine in mice or rats [calingasan-1998-bbb-iron-nos] Induction of nitric oxide synthase and microglial responses precede selective cell death induced by chronic impairment of oxidative metabolism (1998). https://pmc.ncbi.nlm.nih.gov/articles/PMC1852979/ DOI: 10.1016/S0002-9440(10)65602-7

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

Links enzyme-bound iron to vitamin A precursor processing.

evidence_location

Abstract

experimental_model

Site-directed mutant mouse BCO1; cleavage assays and protein-bound iron spectroscopy.

exposure

Individual alanine substitutions at conserved catalytic-site residues.

limitations

Coordination inferred from mutagenesis and iron measurements, not a dietary iron trial.

nutrient_topic

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

organism

Mus musculus recombinant protein

outcome

Substitution of conserved histidines or Glu405 in mouse BCO1 abolished cleavage and reduced protein-bound iron.

plain_language

An intact iron-binding environment is necessary for this enzyme to work.

primary_references

[va-poliakov-2005] Key role of conserved histidines in recombinant mouse beta-carotene 15,15'-monooxygenase-1 activity (2005). https://pubmed.ncbi.nlm.nih.gov/15951442/ DOI: 10.1074/jbc.M500409200

tissue_or_cell_type

Cell-free protein

trigger_kind

machinery_impairment Imported condition classification; unverified.

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 217–230

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Site-directed mutant mouse BCO1; cleavage assays and protein-bound iron spectroscopy. · source_derived_draft · unverified_draft

### va-bco1-iron-binding-machinery Substitution of conserved histidines or Glu405 in mouse BCO1 abolished cleavage and reduced protein-bound iron. Condition category: machinery_impairment nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: An intact iron-binding environment is necessary for this enzyme to work. organism: Mus musculus recombinant protein tissue_or_cell_type: Cell-free protein experimental_model: Site-directed mutant mouse BCO1; cleavage assays and protein-bound iron spectroscopy. limitations: Coordination inferred from mutagenesis and iron measurements, not a dietary iron trial. exposure: Individual alanine substitutions at conserved catalytic-site residues. outcome: Substitution of conserved histidines or Glu405 in mouse BCO1 abolished cleavage and reduced protein-bound iron. evidence_location: Abstract cross_nutrient: Links enzyme-bound iron to vitamin A precursor processing. [va-poliakov-2005] Key role of conserved histidines in recombinant mouse beta-carotene 15,15'-monooxygenase-1 activity (2005). https://pubmed.ncbi.nlm.nih.gov/15951442/ DOI: 10.1074/jbc.M500409200

access_level

selected_primary_main_text_and_legends; cached web/indexed passages, not complete supplement review

evidence_cache

artifacts/discovery-research/round4-sources/s41556-026-01974-0-web.json; SHA256 6971539ed35950faaf1931771badfd7fbad98541e4ffcb56177e63be586de40a

experimental_model

HeLa; MERBiT reporter derivative where stated

exposure

Stable re-expression in HMOX2 KO clone 1; ICP-MS total iron; comparison with wild-type re-expression

limitations

Selected primary main-text Results and figure legends reviewed; supplementary images not independently inspected. These two papers share authors and are not independent replication. They do not test whether SLC25A39-loss-induced contacts increase HMOX2-dependent iron delivery. ICP-MS measures total iron, not labile iron or transport flux. Contact loss affecting an outcome does not establish that increasing contacts increases it. Ubiquitination/activity readouts do not establish direct enzymatic activation or the outer-membrane iron transport machinery. No clinical or pulmonary-endothelial effect is inferred.

organism

Human

primary_locator

Figure 4f

primary_references

https://doi.org/10.1038/s41556-026-01974-0

Glutathione, ER-mitochondria contacts, and iron: observed components · lines 72–80

Targeted primary-literature curation, 2026-09-20. DOIs 10.1038/s41467-025-56666-4 and 10.1038/s41556-026-01974-0. · supports · Human HeLa cells · source_derived_draft · unverified_draft

K68R HMOX2 re-expression failed to restore mitochondrial iron as wild-type HMOX2 did in HMOX2-knockout HeLa cells. primary_references: https://doi.org/10.1038/s41556-026-01974-0 primary_locator: Figure 4f evidence_cache: artifacts/discovery-research/round4-sources/s41556-026-01974-0-web.json; SHA256 6971539ed35950faaf1931771badfd7fbad98541e4ffcb56177e63be586de40a access_level: selected_primary_main_text_and_legends; cached web/indexed passages, not complete supplement review organism: Human experimental_model: HeLa; MERBiT reporter derivative where stated exposure: Stable re-expression in HMOX2 KO clone 1; ICP-MS total iron; comparison with wild-type re-expression limitations: Selected primary main-text Results and figure legends reviewed; supplementary images not independently inspected. These two papers share authors and are not independent replication. They do not test whether SLC25A39-loss-induced contacts increase HMOX2-dependent iron delivery. ICP-MS measures total iron, not labile iron or transport flux. Contact loss affecting an outcome does not establish that increasing contacts increases it. Ubiquitination/activity readouts do not establish direct enzymatic activation or the outer-membrane iron transport machinery. No clinical or pulmonary-endothelial effect is inferred.

access_level

selected_primary_main_text_and_legends; cached web/indexed passages, not complete supplement review

evidence_cache

artifacts/discovery-research/round4-sources/s41556-026-01974-0-web.json; SHA256 6971539ed35950faaf1931771badfd7fbad98541e4ffcb56177e63be586de40a

experimental_model

HeLa; MERBiT reporter derivative where stated

exposure

Stable CRISPR knockout; ICP-MS after digestion; pg iron per microgram mitochondrial protein; three independent experiments

limitations

Selected primary main-text Results and figure legends reviewed; supplementary images not independently inspected. These two papers share authors and are not independent replication. They do not test whether SLC25A39-loss-induced contacts increase HMOX2-dependent iron delivery. ICP-MS measures total iron, not labile iron or transport flux. Contact loss affecting an outcome does not establish that increasing contacts increases it. Ubiquitination/activity readouts do not establish direct enzymatic activation or the outer-membrane iron transport machinery. No clinical or pulmonary-endothelial effect is inferred.

organism

Human

primary_locator

Figure 4c

primary_references

https://doi.org/10.1038/s41556-026-01974-0

Glutathione, ER-mitochondria contacts, and iron: observed components · lines 61–69

Targeted primary-literature curation, 2026-09-20. DOIs 10.1038/s41467-025-56666-4 and 10.1038/s41556-026-01974-0. · supports · Human HeLa cells · source_derived_draft · unverified_draft

HMOX2 knockout reduced total iron measured in isolated HeLa mitochondria. primary_references: https://doi.org/10.1038/s41556-026-01974-0 primary_locator: Figure 4c evidence_cache: artifacts/discovery-research/round4-sources/s41556-026-01974-0-web.json; SHA256 6971539ed35950faaf1931771badfd7fbad98541e4ffcb56177e63be586de40a access_level: selected_primary_main_text_and_legends; cached web/indexed passages, not complete supplement review organism: Human experimental_model: HeLa; MERBiT reporter derivative where stated exposure: Stable CRISPR knockout; ICP-MS after digestion; pg iron per microgram mitochondrial protein; three independent experiments limitations: Selected primary main-text Results and figure legends reviewed; supplementary images not independently inspected. These two papers share authors and are not independent replication. They do not test whether SLC25A39-loss-induced contacts increase HMOX2-dependent iron delivery. ICP-MS measures total iron, not labile iron or transport flux. Contact loss affecting an outcome does not establish that increasing contacts increases it. Ubiquitination/activity readouts do not establish direct enzymatic activation or the outer-membrane iron transport machinery. No clinical or pulmonary-endothelial effect is inferred.

access_level

selected_primary_main_text_and_legends; cached web/indexed passages, not complete supplement review

evidence_cache

artifacts/discovery-research/round4-sources/s41556-026-01974-0-web.json; SHA256 6971539ed35950faaf1931771badfd7fbad98541e4ffcb56177e63be586de40a

experimental_model

HeLa; MERBiT reporter derivative where stated

exposure

Stable CRISPR knockout; ICP-MS after digestion; pg metal per microgram mitochondrial protein; three independent experiments

limitations

Selected primary main-text Results and figure legends reviewed; supplementary images not independently inspected. These two papers share authors and are not independent replication. They do not test whether SLC25A39-loss-induced contacts increase HMOX2-dependent iron delivery. ICP-MS measures total iron, not labile iron or transport flux. Contact loss affecting an outcome does not establish that increasing contacts increases it. Ubiquitination/activity readouts do not establish direct enzymatic activation or the outer-membrane iron transport machinery. No clinical or pulmonary-endothelial effect is inferred.

organism

Human

primary_locator

Figure 4g

primary_references

https://doi.org/10.1038/s41556-026-01974-0

Glutathione, ER-mitochondria contacts, and iron: observed components · lines 83–91

Targeted primary-literature curation, 2026-09-20. DOIs 10.1038/s41467-025-56666-4 and 10.1038/s41556-026-01974-0. · supports · Human HeLa cells · source_derived_draft · unverified_draft

VAPB knockout reduced total iron measured in isolated HeLa mitochondria. primary_references: https://doi.org/10.1038/s41556-026-01974-0 primary_locator: Figure 4g evidence_cache: artifacts/discovery-research/round4-sources/s41556-026-01974-0-web.json; SHA256 6971539ed35950faaf1931771badfd7fbad98541e4ffcb56177e63be586de40a access_level: selected_primary_main_text_and_legends; cached web/indexed passages, not complete supplement review organism: Human experimental_model: HeLa; MERBiT reporter derivative where stated exposure: Stable CRISPR knockout; ICP-MS after digestion; pg metal per microgram mitochondrial protein; three independent experiments limitations: Selected primary main-text Results and figure legends reviewed; supplementary images not independently inspected. These two papers share authors and are not independent replication. They do not test whether SLC25A39-loss-induced contacts increase HMOX2-dependent iron delivery. ICP-MS measures total iron, not labile iron or transport flux. Contact loss affecting an outcome does not establish that increasing contacts increases it. Ubiquitination/activity readouts do not establish direct enzymatic activation or the outer-membrane iron transport machinery. No clinical or pulmonary-endothelial effect is inferred.

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/copper-research/10485908.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2feaccc19bf8f4480643a918de9300a6c224935b47c24e251d96050599e3b067", "start_char": 0, "end_char": 1368, "text_sha256": "2feaccc19bf8f4480643a918de9300a6c224935b47c24e251d96050599e3b067"}

experimental_model

Ceruloplasmin gene disruption and ferrokinetics

exposure

Cp knockout followed through one year

limitations

Genetic ceruloplasmin absence differs from dietary copper shortage; normal intestinal absorption in this experiment does not imply all copper-deficient states absorb iron normally.

nutrient_topic

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

organism

Mouse

plain_language

The main defect was moving stored iron out of cells.

primary_references

[copper-p10485908] Targeted gene disruption reveals an essential role for ceruloplasmin in cellular iron efflux. (1999). https://pubmed.ncbi.nlm.nih.gov/10485908/ DOI: 10.1073/pnas.96.19.10812

tissue_or_cell_type

Liver, spleen and reticuloendothelial cells

trigger_kind

machinery_impairment Imported condition classification; unverified.

Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 793–804

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ceruloplasmin gene disruption and ferrokinetics · source_derived_draft · unverified_draft

### copper-cp-iron-mobilization Cp-null mice had impaired iron release from hepatocytes and reticuloendothelial cells, while measured iron absorption and plasma turnover were comparable to controls. Condition category: machinery_impairment nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: The main defect was moving stored iron out of cells. organism: Mouse tissue_or_cell_type: Liver, spleen and reticuloendothelial cells experimental_model: Ceruloplasmin gene disruption and ferrokinetics limitations: Genetic ceruloplasmin absence differs from dietary copper shortage; normal intestinal absorption in this experiment does not imply all copper-deficient states absorb iron normally. exposure: Cp knockout followed through one year evidence_span: {"source_cache": "artifacts/copper-research/10485908.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2feaccc19bf8f4480643a918de9300a6c224935b47c24e251d96050599e3b067", "start_char": 0, "end_char": 1368, "text_sha256": "2feaccc19bf8f4480643a918de9300a6c224935b47c24e251d96050599e3b067"} [copper-p10485908] Targeted gene disruption reveals an essential role for ceruloplasmin in cellular iron efflux. (1999). https://pubmed.ncbi.nlm.nih.gov/10485908/ DOI: 10.1073/pnas.96.19.10812

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/copper-research/15623839.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5e3723e4fdd961caf66979e26614d98cbfbd65f38ba48232428e5302c054c3ac", "start_char": 0, "end_char": 1613, "text_sha256": "5e3723e4fdd961caf66979e26614d98cbfbd65f38ba48232428e5302c054c3ac"}

experimental_model

Controlled copper-deficient versus adequate diets with radiolabeled iron

exposure

Less than 0.3 versus 5 mg copper/kg diet; male and female weanlings

limitations

Animal depletion regimens are not human thresholds. Iron redistribution differed by sex.

nutrient_topic

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

organism

Rat

plain_language

Adding iron alone does not describe the copper-dependent processing step.

primary_references

[copper-p15623839] Dietary copper deficiency reduces iron absorption and duodenal enterocyte hephaestin protein in male and female rats. (2005). https://pubmed.ncbi.nlm.nih.gov/15623839/ DOI: 10.1093/jn/135.1.92

tissue_or_cell_type

Duodenal enterocytes and whole-body iron

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 871–882

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Controlled copper-deficient versus adequate diets with radiolabeled iron · source_derived_draft · unverified_draft

### copper-cud-iron-absorption Copper-deficient male and female rats absorbed about 60% and 70%, respectively, of the iron absorbed by copper-adequate controls. Condition category: nutrient_deficiency nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Adding iron alone does not describe the copper-dependent processing step. organism: Rat tissue_or_cell_type: Duodenal enterocytes and whole-body iron experimental_model: Controlled copper-deficient versus adequate diets with radiolabeled iron limitations: Animal depletion regimens are not human thresholds. Iron redistribution differed by sex. exposure: Less than 0.3 versus 5 mg copper/kg diet; male and female weanlings evidence_span: {"source_cache": "artifacts/copper-research/15623839.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5e3723e4fdd961caf66979e26614d98cbfbd65f38ba48232428e5302c054c3ac", "start_char": 0, "end_char": 1613, "text_sha256": "5e3723e4fdd961caf66979e26614d98cbfbd65f38ba48232428e5302c054c3ac"} [copper-p15623839] Dietary copper deficiency reduces iron absorption and duodenal enterocyte hephaestin protein in male and female rats. (2005). https://pubmed.ncbi.nlm.nih.gov/15623839/ DOI: 10.1093/jn/135.1.92

evidence_span

{"source_cache": "artifacts/copper-research/27714044.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5e8791edb75475ba74e95cddc330c06512ef3b9c02a0c5a6b203327c047dff37", "start_char": 0, "end_char": 1780, "text_sha256": "5e8791edb75475ba74e95cddc330c06512ef3b9c02a0c5a6b203327c047dff37"}

experimental_model

ATP7A knockdown in differentiated intestinal cell cultures

exposure

ATP7A knockdown and radiolabeled iron transport

limitations

Reductionist cell models; increased enzyme activity did not guarantee increased net iron flux. Molecular expression details were measured in the rat line.

nutrient_topic

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

organism

Human

plain_language

A copper transporter also helps the intestinal iron-handling system function.

primary_references

[copper-p27714044] Knockdown of copper-transporting ATPase 1 (Atp7a) impairs iron flux in fully-differentiated rat (IEC-6) and human (Caco-2) intestinal epithelial cells. (2016). https://pubmed.ncbi.nlm.nih.gov/27714044/ DOI: 10.1039/c6mt00126b

tissue_or_cell_type

Caco-2 cells

Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 897–908

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · ATP7A knockdown in differentiated intestinal cell cultures · source_derived_draft · unverified_draft

### copper-human-atp7a-iron ATP7A silencing impaired iron uptake and efflux in differentiated human Caco-2 cells. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: A copper transporter also helps the intestinal iron-handling system function. organism: Human tissue_or_cell_type: Caco-2 cells experimental_model: ATP7A knockdown in differentiated intestinal cell cultures limitations: Reductionist cell models; increased enzyme activity did not guarantee increased net iron flux. Molecular expression details were measured in the rat line. exposure: ATP7A knockdown and radiolabeled iron transport evidence_span: {"source_cache": "artifacts/copper-research/27714044.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5e8791edb75475ba74e95cddc330c06512ef3b9c02a0c5a6b203327c047dff37", "start_char": 0, "end_char": 1780, "text_sha256": "5e8791edb75475ba74e95cddc330c06512ef3b9c02a0c5a6b203327c047dff37"} [copper-p27714044] Knockdown of copper-transporting ATPase 1 (Atp7a) impairs iron flux in fully-differentiated rat (IEC-6) and human (Caco-2) intestinal epithelial cells. (2016). https://pubmed.ncbi.nlm.nih.gov/27714044/ DOI: 10.1039/c6mt00126b

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/copper-research/16950140.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "08532f69fd9530033f8d9afcece9249fc50dd425f57313e120f55ea81cee8f98", "start_char": 0, "end_char": 1026, "text_sha256": "08532f69fd9530033f8d9afcece9249fc50dd425f57313e120f55ea81cee8f98"}

experimental_model

Intestinal epithelial Ctr1 knockout mice

exposure

Intestinal Ctr1 deletion; postnatal copper rescue

limitations

Genetic intestinal transport failure differs from low dietary intake. The indexed abstract does not establish the administration route of the rescue dose.

nutrient_topic

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

organism

Mouse

plain_language

A copper transport defect also disrupted where iron accumulated.

primary_references

[copper-p16950140] Ctr1 drives intestinal copper absorption and is essential for growth, iron metabolism, and neonatal cardiac function. (2006). https://pubmed.ncbi.nlm.nih.gov/16950140/ DOI: 10.1016/j.cmet.2006.08.009

tissue_or_cell_type

Intestine and peripheral organs

trigger_kind

machinery_impairment Imported condition classification; unverified.

Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 325–336

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Intestinal epithelial Ctr1 knockout mice · source_derived_draft · unverified_draft

### copper-intestinal-ctr1-iron Mice lacking intestinal Ctr1 developed hepatic iron overload alongside systemic copper deficiency. Condition category: machinery_impairment nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: A copper transport defect also disrupted where iron accumulated. organism: Mouse tissue_or_cell_type: Intestine and peripheral organs experimental_model: Intestinal epithelial Ctr1 knockout mice limitations: Genetic intestinal transport failure differs from low dietary intake. The indexed abstract does not establish the administration route of the rescue dose. exposure: Intestinal Ctr1 deletion; postnatal copper rescue evidence_span: {"source_cache": "artifacts/copper-research/16950140.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "08532f69fd9530033f8d9afcece9249fc50dd425f57313e120f55ea81cee8f98", "start_char": 0, "end_char": 1026, "text_sha256": "08532f69fd9530033f8d9afcece9249fc50dd425f57313e120f55ea81cee8f98"} [copper-p16950140] Ctr1 drives intestinal copper absorption and is essential for growth, iron metabolism, and neonatal cardiac function. (2006). https://pubmed.ncbi.nlm.nih.gov/16950140/ DOI: 10.1016/j.cmet.2006.08.009

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

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/copper-research/42308035.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0c19d3c109f1df88791ad51c22e6acf85b7d5ffe5c26c74aaaf5e3222a75c054", "start_char": 4157, "end_char": 4553, "text_sha256": "458c46d27cddab000b77009e2f8f1d373871eaa90d0571867d421984ecd9803a"}

experimental_model

Rat Slc25a3 knockout cardiomyoblasts and human transporter expression in bacteria

exposure

Slc25a3 deletion and elesclomol-copper exposure

limitations

Whole-organelle copper was measured, not separate matrix and intermembrane pools. Matrix trapping is the authors mechanism inferred with transport evidence. This recent study complements import findings; bacterial export does not reproduce mitochondrial topology.

nutrient_topic

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

organism

Rat H9c2 cells; human SLC25A3 in Lactococcus lactis

plain_language

Copper misrouting also affected enzymes that depend on iron-sulfur clusters.

primary_references

[copper-p42308035] SLC25A3 exports mitochondrial copper to metalate cytochrome c oxidase and prevent cuproptosis. (2026). https://pubmed.ncbi.nlm.nih.gov/42308035/ DOI: 10.1073/pnas.2612098123

tissue_or_cell_type

Mitochondria; bacterial copper export assay

trigger_kind

machinery_impairment Imported condition classification; unverified.

Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 585–596

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat Slc25a3 knockout cardiomyoblasts and human transporter expression in bacteria · source_derived_draft · unverified_draft

### copper-slc25a3-es-fe-s Elesclomol-copper reduced the iron-sulfur proteins SDHB and ACO2 in Slc25a3-null rat cells. Condition category: machinery_impairment nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Copper misrouting also affected enzymes that depend on iron-sulfur clusters. organism: Rat H9c2 cells; human SLC25A3 in Lactococcus lactis tissue_or_cell_type: Mitochondria; bacterial copper export assay experimental_model: Rat Slc25a3 knockout cardiomyoblasts and human transporter expression in bacteria limitations: Whole-organelle copper was measured, not separate matrix and intermembrane pools. Matrix trapping is the authors mechanism inferred with transport evidence. This recent study complements import findings; bacterial export does not reproduce mitochondrial topology. exposure: Slc25a3 deletion and elesclomol-copper exposure evidence_span: {"source_cache": "artifacts/copper-research/42308035.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0c19d3c109f1df88791ad51c22e6acf85b7d5ffe5c26c74aaaf5e3222a75c054", "start_char": 4157, "end_char": 4553, "text_sha256": "458c46d27cddab000b77009e2f8f1d373871eaa90d0571867d421984ecd9803a"} [copper-p42308035] SLC25A3 exports mitochondrial copper to metalate cytochrome c oxidase and prevent cuproptosis. (2026). https://pubmed.ncbi.nlm.nih.gov/42308035/ DOI: 10.1073/pnas.2612098123

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

B6-drug conjugation connects to iron-sensitive heme machinery.

experimental_model

Cell-free chemistry, primary human hepatocytes and HepG2/C3A cells

exposure

100 micromolar PIH for 16 hours in the initial HepG2/C3A comparison; 24-hour PIH dose-response assays.

limitations

Direct destruction of the FECH iron-sulfur cluster was not demonstrated.

nutrient_topic

Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6

organism

Homo sapiens

plain_language

A drug-B6 conjugate affected a heme-making enzyme.

primary_references

[brewer-2019-isoniazid] The Isoniazid Metabolites Hydrazine and Pyridoxal Isonicotinoyl Hydrazone Modulate Heme Biosynthesis (2019). https://pmc.ncbi.nlm.nih.gov/articles/PMC6390808/ DOI: 10.1093/toxsci/kfy294

tissue_or_cell_type

Primary human hepatocytes and HepG2/C3A cells

trigger_kind

machinery_impairment Imported condition classification; unverified.

Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1296–1307

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell-free chemistry, primary human hepatocytes and HepG2/C3A cells · source_derived_draft · unverified_draft

### b6-neuro-pih-fech-protein PIH treatment lowered FECH protein without lowering FECH mRNA in human liver-cell models. Condition category: machinery_impairment nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A drug-B6 conjugate affected a heme-making enzyme. organism: Homo sapiens tissue_or_cell_type: Primary human hepatocytes and HepG2/C3A cells experimental_model: Cell-free chemistry, primary human hepatocytes and HepG2/C3A cells limitations: Direct destruction of the FECH iron-sulfur cluster was not demonstrated. exposure: 100 micromolar PIH for 16 hours in the initial HepG2/C3A comparison; 24-hour PIH dose-response assays. cross_nutrient: B6-drug conjugation connects to iron-sensitive heme machinery. [brewer-2019-isoniazid] The Isoniazid Metabolites Hydrazine and Pyridoxal Isonicotinoyl Hydrazone Modulate Heme Biosynthesis (2019). https://pmc.ncbi.nlm.nih.gov/articles/PMC6390808/ DOI: 10.1093/toxsci/kfy294

cross_nutrient

true

evidence_location

Primary abstract and structure PDB 3C6G.

experimental_model

Purified human enzyme crystallography

exposure

CYP2R1-D3 crystal complex; PDB 3C6G.

limitations

A structural iron requirement is not evidence that iron supplements increase vitamin D activation in iron-replete people.

nutrient

Vitamin D2 and D3 · Vitamin D2 and D3

nutrient_topic

Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin D2 and D3

organism

Homo sapiens protein

plain_language

D3 activation uses an iron-containing heme enzyme.

primary_references

[strushkevich2008] Structural analysis of CYP2R1 in complex with vitamin D3. (2008). https://pubmed.ncbi.nlm.nih.gov/18511070/ DOI: 10.1016/j.jmb.2008.03.065

tissue_or_cell_type

CYP2R1 active site

Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 377–390

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human enzyme crystallography · source_derived_draft · unverified_draft

### vd-act-cyp2r1-heme The human CYP2R1-D3 structure contained heme, with the vitamin D3 side chain directed toward this catalytic prosthetic group. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: D3 activation uses an iron-containing heme enzyme. organism: Homo sapiens protein tissue_or_cell_type: CYP2R1 active site experimental_model: Purified human enzyme crystallography limitations: A structural iron requirement is not evidence that iron supplements increase vitamin D activation in iron-replete people. exposure: CYP2R1-D3 crystal complex; PDB 3C6G. cross_nutrient: true evidence_location: Primary abstract and structure PDB 3C6G. nutrient: Vitamin D2 and D3 [strushkevich2008] Structural analysis of CYP2R1 in complex with vitamin D3. (2008). https://pubmed.ncbi.nlm.nih.gov/18511070/ DOI: 10.1016/j.jmb.2008.03.065

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Local iron storage changes accompany severe thiamine disruption; this is not evidence of systemic iron deficiency or overload.

evidence_location

Results: Ferritin, Iron, and Microglial Responses to TD; Figures 5-6

evidence_span

intense ferritin immunoreactivity

experimental_model

Adult male C57BL/6 mice and Fischer 344 Brown Norway F1 rats; thiamine-deficient diet plus pyrithiamine 0.5 mg/kg/day intraperitoneally; staged brain histochemistry.

exposure

Dietary thiamine removal plus daily pyrithiamine in mice or rats

limitations

Staining does not distinguish ferritin subunits or prove ferritin causes injury; serum ferritin was not measured.

nutrient_topic

Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)

organism

Mus musculus; Rattus norvegicus

plain_language

Iron-storage protein accumulated locally alongside the iron signal.

primary_references

[calingasan-1998-bbb-iron-nos] Induction of nitric oxide synthase and microglial responses precede selective cell death induced by chronic impairment of oxidative metabolism (1998). https://pmc.ncbi.nlm.nih.gov/articles/PMC1852979/ DOI: 10.1016/S0002-9440(10)65602-7

tissue_or_cell_type

Vulnerable brain microglia and microvessels

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1240–1253

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Adult male C57BL/6 mice and Fischer 344 Brown Norway F1 rats; thiamine-deficient diet plus pyrithiamine 0.5 mg/kg/day intraperitoneally; staged brain histochemistry. · source_derived_draft · unverified_draft

### thiamine-def-ferritin-regional-increase Ferritin staining increased in activated microglia and vessels within selectively vulnerable regions of depleted mice and rats. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Iron-storage protein accumulated locally alongside the iron signal. organism: Mus musculus; Rattus norvegicus tissue_or_cell_type: Vulnerable brain microglia and microvessels experimental_model: Adult male C57BL/6 mice and Fischer 344 Brown Norway F1 rats; thiamine-deficient diet plus pyrithiamine 0.5 mg/kg/day intraperitoneally; staged brain histochemistry. limitations: Staining does not distinguish ferritin subunits or prove ferritin causes injury; serum ferritin was not measured. evidence_location: Results: Ferritin, Iron, and Microglial Responses to TD; Figures 5-6 evidence_span: intense ferritin immunoreactivity cross_nutrient: Local iron storage changes accompany severe thiamine disruption; this is not evidence of systemic iron deficiency or overload. exposure: Dietary thiamine removal plus daily pyrithiamine in mice or rats [calingasan-1998-bbb-iron-nos] Induction of nitric oxide synthase and microglial responses precede selective cell death induced by chronic impairment of oxidative metabolism (1998). https://pmc.ncbi.nlm.nih.gov/articles/PMC1852979/ DOI: 10.1016/S0002-9440(10)65602-7

evidence_span

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experimental_model

Cells with defined intracellular ascorbate concentrations against several hydroxylase inhibitors

exposure

Intracellular ascorbate loading with CoCl2, NiCl2, desferrioxamine, dimethyloxalylglycine or hypoxia

limitations

Establishes an effect of intracellular ascorbate on the HIF response. The iron-competing inhibitors are the conditions where ascorbate mattered most.

nutrient_topic

Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

organism

Human cells

plain_language

Vitamin C shuts down the low-oxygen gene programme even when the protein itself survives.

primary_references

[hbot-p24495550] Intracellular ascorbate enhances hypoxia-inducible factor (HIF)-hydroxylase activity and preferentially suppresses the HIF-1 transcriptional response. (2014). https://pubmed.ncbi.nlm.nih.gov/24495550/ DOI: 10.1016/j.freeradbiomed.2014.01.033

tissue_or_cell_type

Cytosol and nucleus

Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 985–996

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cells with defined intracellular ascorbate concentrations against several hydroxylase inhibitors · source_derived_draft · unverified_draft

### hbot-ascorbate-suppresses-hif Ascorbate inhibited HIF-1 activity most dramatically under all mechanisms of iron competition, and HIF-1-dependent gene expression was prevented even under conditions that allowed HIF-1alpha protein stabilisation. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Vitamin C shuts down the low-oxygen gene programme even when the protein itself survives. organism: Human cells tissue_or_cell_type: Cytosol and nucleus experimental_model: Cells with defined intracellular ascorbate concentrations against several hydroxylase inhibitors limitations: Establishes an effect of intracellular ascorbate on the HIF response. The iron-competing inhibitors are the conditions where ascorbate mattered most. exposure: Intracellular ascorbate loading with CoCl2, NiCl2, desferrioxamine, dimethyloxalylglycine or hypoxia evidence_span: {"source_cache": "artifacts/hbot-research/24495550.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "444b204ff84635f64eebf59c2db6afa112641b24f7b309fb2bcd6da04d4d0d0a", "start_char": 0, "end_char": 1497, "text_sha256": "444b204ff84635f64eebf59c2db6afa112641b24f7b309fb2bcd6da04d4d0d0a"} [hbot-p24495550] Intracellular ascorbate enhances hypoxia-inducible factor (HIF)-hydroxylase activity and preferentially suppresses the HIF-1 transcriptional response. (2014). https://pubmed.ncbi.nlm.nih.gov/24495550/ DOI: 10.1016/j.freeradbiomed.2014.01.033

evidence_span

{"source_cache": "artifacts/hbot-research/15642322.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e3bc035a17e4e19dd92d4fadb1a79f8e3801619dac24fb91dcf985728afaf995", "start_char": 0, "end_char": 2646, "text_sha256": "e3bc035a17e4e19dd92d4fadb1a79f8e3801619dac24fb91dcf985728afaf995"}

experimental_model

Cultured human lens epithelial cells exposed to extreme hyperbaric oxygen with enzyme assays and real-time PCR

exposure

99% oxygen at 50 atmospheres for 3 hours, then normal culture for up to 11 days

limitations

Fifty atmospheres is an extreme experimental exposure far above therapy, chosen to probe which defences matter. The selenoenzyme result is the informative part; the pressure is not clinically relevant.

nutrient_topic

Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

organism

Human cells

plain_language

Iron freed from heme may be the signal that calls up the manganese enzyme.

primary_references

[hbot-p15642322] Thioredoxin reductase may be essential for the normal growth of hyperbaric oxygen-treated human lens epithelial cells. (2004). https://pubmed.ncbi.nlm.nih.gov/15642322/ DOI: 10.1016/j.exer.2004.07.001

tissue_or_cell_type

Lens epithelium

Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 439–450

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cultured human lens epithelial cells exposed to extreme hyperbaric oxygen with enzyme assays and real-time PCR · source_derived_draft · unverified_draft

### hbot-ho1-iron-to-mnsod The authors suggest that release of free iron from the degradation of heme by heme oxygenase-1 may have played a role in the later upregulation of the manganese dismutase. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Iron freed from heme may be the signal that calls up the manganese enzyme. organism: Human cells tissue_or_cell_type: Lens epithelium experimental_model: Cultured human lens epithelial cells exposed to extreme hyperbaric oxygen with enzyme assays and real-time PCR limitations: Fifty atmospheres is an extreme experimental exposure far above therapy, chosen to probe which defences matter. The selenoenzyme result is the informative part; the pressure is not clinically relevant. exposure: 99% oxygen at 50 atmospheres for 3 hours, then normal culture for up to 11 days evidence_span: {"source_cache": "artifacts/hbot-research/15642322.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e3bc035a17e4e19dd92d4fadb1a79f8e3801619dac24fb91dcf985728afaf995", "start_char": 0, "end_char": 2646, "text_sha256": "e3bc035a17e4e19dd92d4fadb1a79f8e3801619dac24fb91dcf985728afaf995"} [hbot-p15642322] Thioredoxin reductase may be essential for the normal growth of hyperbaric oxygen-treated human lens epithelial cells. (2004). https://pubmed.ncbi.nlm.nih.gov/15642322/ DOI: 10.1016/j.exer.2004.07.001

evidence_span

{"source_cache": "artifacts/hbot-research/11023535.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "19b770dff3d327e2dd6d49180686f9823624190ab5693c28b88adcfaf703f14d", "start_char": 0, "end_char": 1576, "text_sha256": "19b770dff3d327e2dd6d49180686f9823624190ab5693c28b88adcfaf703f14d"}

experimental_model

Comet assay in lymphocytes of volunteers before and after hyperbaric oxygen, with enzyme expression measurement

exposure

100% oxygen at 2.5 ATA for three 20-minute periods

limitations

A human exposure study with a within-subject design. The iron-sequestration explanation is the authors’ inference from the pattern of protection, not a direct measurement of free iron.

nutrient_topic

Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

organism

Human

plain_language

The proposed protection is locking away the iron that would otherwise turn peroxide into a more dangerous radical.

primary_references

[hbot-p11023535] Induction of heme oxygenase-1 and adaptive protection against the induction of DNA damage after hyperbaric oxygen treatment. (2000). https://pubmed.ncbi.nlm.nih.gov/11023535/ DOI: 10.1093/carcin/21.10.1795

tissue_or_cell_type

Circulating lymphocytes

Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 322–333

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Comet assay in lymphocytes of volunteers before and after hyperbaric oxygen, with enzyme expression measurement · source_derived_draft · unverified_draft

### hbot-iron-sequestration-hypothesis The authors suggest that increased sequestration of iron as a consequence of induced heme oxygenase-1 might be involved in the adaptive protection, and that induction of DNA damage is not the trigger for it. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: The proposed protection is locking away the iron that would otherwise turn peroxide into a more dangerous radical. organism: Human tissue_or_cell_type: Circulating lymphocytes experimental_model: Comet assay in lymphocytes of volunteers before and after hyperbaric oxygen, with enzyme expression measurement limitations: A human exposure study with a within-subject design. The iron-sequestration explanation is the authors’ inference from the pattern of protection, not a direct measurement of free iron. exposure: 100% oxygen at 2.5 ATA for three 20-minute periods evidence_span: {"source_cache": "artifacts/hbot-research/11023535.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "19b770dff3d327e2dd6d49180686f9823624190ab5693c28b88adcfaf703f14d", "start_char": 0, "end_char": 1576, "text_sha256": "19b770dff3d327e2dd6d49180686f9823624190ab5693c28b88adcfaf703f14d"} [hbot-p11023535] Induction of heme oxygenase-1 and adaptive protection against the induction of DNA damage after hyperbaric oxygen treatment. (2000). https://pubmed.ncbi.nlm.nih.gov/11023535/ DOI: 10.1093/carcin/21.10.1795

evidence_span

{"source_cache": "artifacts/chromium-research/9322572.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "767fd4144862b2bbc3bf416541442924fc69da030435898b1e6843dba8e35dc8", "start_char": 0, "end_char": 1869, "text_sha256": "767fd4144862b2bbc3bf416541442924fc69da030435898b1e6843dba8e35dc8"}

experimental_model

Randomized double-blind supplementation with resistance training; 18 men

exposure

924 µg chromium/day as picolinate versus placebo for 12 weeks; nine men/group

limitations

Small selected population and short follow-up. A negative result does not exclude every interaction in iron-deficient people or other exposures.

nutrient_topic

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

organism

Human men aged 56–69

plain_language

The proposed iron-depleting effect was not observed in these older men.

primary_references

[chromium-p9322572] Chromium picolinate supplementation and resistive training by older men: effects on iron-status and hematologic indexes. (1997). https://pubmed.ncbi.nlm.nih.gov/9322572/ DOI: 10.1093/ajcn/66.4.944

tissue_or_cell_type

Iron-status and hematologic indices

Chromium: transport, insulin signaling, nutrient interactions and essentiality debate (2026-09-17) · lines 536–547

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized double-blind supplementation with resistance training; 18 men · source_derived_draft · unverified_draft

### chromium-human-iron-status-null Chromium picolinate did not change the measured hematologic indices, serum iron or ferritin relative to placebo during the training study. Condition category: normal nutrient_topic: Chromium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The proposed iron-depleting effect was not observed in these older men. organism: Human men aged 56–69 tissue_or_cell_type: Iron-status and hematologic indices experimental_model: Randomized double-blind supplementation with resistance training; 18 men limitations: Small selected population and short follow-up. A negative result does not exclude every interaction in iron-deficient people or other exposures. exposure: 924 µg chromium/day as picolinate versus placebo for 12 weeks; nine men/group evidence_span: {"source_cache": "artifacts/chromium-research/9322572.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "767fd4144862b2bbc3bf416541442924fc69da030435898b1e6843dba8e35dc8", "start_char": 0, "end_char": 1869, "text_sha256": "767fd4144862b2bbc3bf416541442924fc69da030435898b1e6843dba8e35dc8"} [chromium-p9322572] Chromium picolinate supplementation and resistive training by older men: effects on iron-status and hematologic indexes. (1997). https://pubmed.ncbi.nlm.nih.gov/9322572/ DOI: 10.1093/ajcn/66.4.944

evidence_span

{"source_cache": "artifacts/chromium-research/9322572.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "767fd4144862b2bbc3bf416541442924fc69da030435898b1e6843dba8e35dc8", "start_char": 0, "end_char": 1869, "text_sha256": "767fd4144862b2bbc3bf416541442924fc69da030435898b1e6843dba8e35dc8"}

experimental_model

Randomized double-blind supplementation with resistance training; 18 men

exposure

924 µg chromium/day as picolinate versus placebo for 12 weeks; nine men/group

limitations

Small selected population and short follow-up. A negative result does not exclude every interaction in iron-deficient people or other exposures.

nutrient_topic

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

organism

Human men aged 56–69

plain_language

Sharing carrier chemistry did not translate into a detectable adverse iron-transport effect in this trial.

primary_references

[chromium-p9322572] Chromium picolinate supplementation and resistive training by older men: effects on iron-status and hematologic indexes. (1997). https://pubmed.ncbi.nlm.nih.gov/9322572/ DOI: 10.1093/ajcn/66.4.944

tissue_or_cell_type

Iron-status and hematologic indices

Chromium: transport, insulin signaling, nutrient interactions and essentiality debate (2026-09-17) · lines 549–560

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized double-blind supplementation with resistance training; 18 men · source_derived_draft · unverified_draft

### chromium-human-transferrin-saturation-null Chromium picolinate did not alter the training-associated changes in total iron-binding capacity or transferrin saturation. Condition category: normal nutrient_topic: Chromium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Sharing carrier chemistry did not translate into a detectable adverse iron-transport effect in this trial. organism: Human men aged 56–69 tissue_or_cell_type: Iron-status and hematologic indices experimental_model: Randomized double-blind supplementation with resistance training; 18 men limitations: Small selected population and short follow-up. A negative result does not exclude every interaction in iron-deficient people or other exposures. exposure: 924 µg chromium/day as picolinate versus placebo for 12 weeks; nine men/group evidence_span: {"source_cache": "artifacts/chromium-research/9322572.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "767fd4144862b2bbc3bf416541442924fc69da030435898b1e6843dba8e35dc8", "start_char": 0, "end_char": 1869, "text_sha256": "767fd4144862b2bbc3bf416541442924fc69da030435898b1e6843dba8e35dc8"} [chromium-p9322572] Chromium picolinate supplementation and resistive training by older men: effects on iron-status and hematologic indexes. (1997). https://pubmed.ncbi.nlm.nih.gov/9322572/ DOI: 10.1093/ajcn/66.4.944

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/chromium-research/29173471.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9de0b60d39b67304da3d1042ebc5f1ed5622a5675e6a0cda4c531bf64249ef2e", "start_char": 0, "end_char": 1448, "text_sha256": "9de0b60d39b67304da3d1042ebc5f1ed5622a5675e6a0cda4c531bf64249ef2e"}

experimental_model

Six-week factorial chromium/iron feeding study

exposure

Iron at 10% versus 100% of the study reference level; chromium propionate at 1, 50 or 500 mg Cr/kg diet

limitations

Very high chromium doses in an animal experiment. Changes do not establish a recommended human ratio, a chromium rescue for anemia or a universal competition rule.

nutrient_topic

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

organism

Female Wistar rats

plain_language

This animal experiment did not show the predicted worsening of iron status.

primary_references

[chromium-p29173471] The combined effect of supplementary Cr(III) propionate complex and iron deficiency on the chromium and iron status in female rats. (2018). https://pubmed.ncbi.nlm.nih.gov/29173471/ DOI: 10.1016/j.jtemb.2017.10.010

tissue_or_cell_type

Tissue metals and hematologic indices

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Chromium: transport, insulin signaling, nutrient interactions and essentiality debate (2026-09-17) · lines 497–508

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Six-week factorial chromium/iron feeding study · source_derived_draft · unverified_draft

### chromium-iron-deficiency-not-worsened High chromium-propionate supplementation did not deepen the measured adverse iron-status and hematologic changes from iron restriction. Condition category: nutrient_deficiency nutrient_topic: Chromium research collection; topical membership is not evidence of a direct dietary effect. plain_language: This animal experiment did not show the predicted worsening of iron status. organism: Female Wistar rats tissue_or_cell_type: Tissue metals and hematologic indices experimental_model: Six-week factorial chromium/iron feeding study limitations: Very high chromium doses in an animal experiment. Changes do not establish a recommended human ratio, a chromium rescue for anemia or a universal competition rule. exposure: Iron at 10% versus 100% of the study reference level; chromium propionate at 1, 50 or 500 mg Cr/kg diet evidence_span: {"source_cache": "artifacts/chromium-research/29173471.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9de0b60d39b67304da3d1042ebc5f1ed5622a5675e6a0cda4c531bf64249ef2e", "start_char": 0, "end_char": 1448, "text_sha256": "9de0b60d39b67304da3d1042ebc5f1ed5622a5675e6a0cda4c531bf64249ef2e"} [chromium-p29173471] The combined effect of supplementary Cr(III) propionate complex and iron deficiency on the chromium and iron status in female rats. (2018). https://pubmed.ncbi.nlm.nih.gov/29173471/ DOI: 10.1016/j.jtemb.2017.10.010

evidence_span

{"source_cache": "artifacts/chromium-research/41108476.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7c71767b7a3b58e61b7961f55febf9d637807fe598539f4257a3b1e40fe03fb3", "start_char": 0, "end_char": 1865, "text_sha256": "7c71767b7a3b58e61b7961f55febf9d637807fe598539f4257a3b1e40fe03fb3"}

experimental_model

Five-group iron-excess supplementation experiment; 30 rats

exposure

Eight weeks; adequate or excessive iron as iron citrate with three chromium-picolinate dose levels

limitations

Small animal experiment with multiple measured changes. Pathway mediation was proposed, not established by a complete intervention on each signaling node; no human treatment or dietary rescue claim.

nutrient_topic

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

organism

Male Wistar rats

plain_language

A measured component of the cell-death response was lower.

primary_references

[chromium-p41108476] Chromium Mitigates the Iron-Induced Glucose Metabolism Disorder via the PI3K/Akt/Bcl-2 Signaling Pathway: An In Vivo Study in Wistar Rats. (2026). https://pubmed.ncbi.nlm.nih.gov/41108476/ DOI: 10.1007/s12011-025-04867-9

tissue_or_cell_type

Pancreatic tissue and systemic glucose measures

Chromium: transport, insulin signaling, nutrient interactions and essentiality debate (2026-09-17) · lines 835–846

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Five-group iron-excess supplementation experiment; 30 rats · source_derived_draft · unverified_draft

### chromium-iron-rat-bax Chromium treatment countered the iron-associated increase in pancreatic Bax. Condition category: normal nutrient_topic: Chromium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A measured component of the cell-death response was lower. organism: Male Wistar rats tissue_or_cell_type: Pancreatic tissue and systemic glucose measures experimental_model: Five-group iron-excess supplementation experiment; 30 rats limitations: Small animal experiment with multiple measured changes. Pathway mediation was proposed, not established by a complete intervention on each signaling node; no human treatment or dietary rescue claim. exposure: Eight weeks; adequate or excessive iron as iron citrate with three chromium-picolinate dose levels evidence_span: {"source_cache": "artifacts/chromium-research/41108476.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7c71767b7a3b58e61b7961f55febf9d637807fe598539f4257a3b1e40fe03fb3", "start_char": 0, "end_char": 1865, "text_sha256": "7c71767b7a3b58e61b7961f55febf9d637807fe598539f4257a3b1e40fe03fb3"} [chromium-p41108476] Chromium Mitigates the Iron-Induced Glucose Metabolism Disorder via the PI3K/Akt/Bcl-2 Signaling Pathway: An In Vivo Study in Wistar Rats. (2026). https://pubmed.ncbi.nlm.nih.gov/41108476/ DOI: 10.1007/s12011-025-04867-9

evidence_span

{"source_cache": "artifacts/chromium-research/41108476.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7c71767b7a3b58e61b7961f55febf9d637807fe598539f4257a3b1e40fe03fb3", "start_char": 0, "end_char": 1865, "text_sha256": "7c71767b7a3b58e61b7961f55febf9d637807fe598539f4257a3b1e40fe03fb3"}

experimental_model

Five-group iron-excess supplementation experiment; 30 rats

exposure

Eight weeks; adequate or excessive iron as iron citrate with three chromium-picolinate dose levels

limitations

Small animal experiment with multiple measured changes. Pathway mediation was proposed, not established by a complete intervention on each signaling node; no human treatment or dietary rescue claim.

nutrient_topic

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

organism

Male Wistar rats

plain_language

A protein associated with cell survival was better preserved.

primary_references

[chromium-p41108476] Chromium Mitigates the Iron-Induced Glucose Metabolism Disorder via the PI3K/Akt/Bcl-2 Signaling Pathway: An In Vivo Study in Wistar Rats. (2026). https://pubmed.ncbi.nlm.nih.gov/41108476/ DOI: 10.1007/s12011-025-04867-9

tissue_or_cell_type

Pancreatic tissue and systemic glucose measures

Chromium: transport, insulin signaling, nutrient interactions and essentiality debate (2026-09-17) · lines 822–833

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Five-group iron-excess supplementation experiment; 30 rats · source_derived_draft · unverified_draft

### chromium-iron-rat-bcl2 Chromium treatment countered the iron-associated reduction in pancreatic Bcl-2. Condition category: normal nutrient_topic: Chromium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A protein associated with cell survival was better preserved. organism: Male Wistar rats tissue_or_cell_type: Pancreatic tissue and systemic glucose measures experimental_model: Five-group iron-excess supplementation experiment; 30 rats limitations: Small animal experiment with multiple measured changes. Pathway mediation was proposed, not established by a complete intervention on each signaling node; no human treatment or dietary rescue claim. exposure: Eight weeks; adequate or excessive iron as iron citrate with three chromium-picolinate dose levels evidence_span: {"source_cache": "artifacts/chromium-research/41108476.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7c71767b7a3b58e61b7961f55febf9d637807fe598539f4257a3b1e40fe03fb3", "start_char": 0, "end_char": 1865, "text_sha256": "7c71767b7a3b58e61b7961f55febf9d637807fe598539f4257a3b1e40fe03fb3"} [chromium-p41108476] Chromium Mitigates the Iron-Induced Glucose Metabolism Disorder via the PI3K/Akt/Bcl-2 Signaling Pathway: An In Vivo Study in Wistar Rats. (2026). https://pubmed.ncbi.nlm.nih.gov/41108476/ DOI: 10.1007/s12011-025-04867-9

evidence_span

{"source_cache": "artifacts/chromium-research/41108476.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7c71767b7a3b58e61b7961f55febf9d637807fe598539f4257a3b1e40fe03fb3", "start_char": 0, "end_char": 1865, "text_sha256": "7c71767b7a3b58e61b7961f55febf9d637807fe598539f4257a3b1e40fe03fb3"}

experimental_model

Five-group iron-excess supplementation experiment; 30 rats

exposure

Eight weeks; adequate or excessive iron as iron citrate with three chromium-picolinate dose levels

limitations

Small animal experiment with multiple measured changes. Pathway mediation was proposed, not established by a complete intervention on each signaling node; no human treatment or dietary rescue claim.

nutrient_topic

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

organism

Male Wistar rats

plain_language

The iron-challenged rats showed less pancreatic-cell injury with chromium treatment.

primary_references

[chromium-p41108476] Chromium Mitigates the Iron-Induced Glucose Metabolism Disorder via the PI3K/Akt/Bcl-2 Signaling Pathway: An In Vivo Study in Wistar Rats. (2026). https://pubmed.ncbi.nlm.nih.gov/41108476/ DOI: 10.1007/s12011-025-04867-9

tissue_or_cell_type

Pancreatic tissue and systemic glucose measures

Chromium: transport, insulin signaling, nutrient interactions and essentiality debate (2026-09-17) · lines 809–820

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Five-group iron-excess supplementation experiment; 30 rats · source_derived_draft · unverified_draft

### chromium-iron-rat-beta-cell-apoptosis Chromium picolinate attenuated the pancreatic beta-cell apoptosis associated with iron excess in the rat experiment. Condition category: normal nutrient_topic: Chromium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The iron-challenged rats showed less pancreatic-cell injury with chromium treatment. organism: Male Wistar rats tissue_or_cell_type: Pancreatic tissue and systemic glucose measures experimental_model: Five-group iron-excess supplementation experiment; 30 rats limitations: Small animal experiment with multiple measured changes. Pathway mediation was proposed, not established by a complete intervention on each signaling node; no human treatment or dietary rescue claim. exposure: Eight weeks; adequate or excessive iron as iron citrate with three chromium-picolinate dose levels evidence_span: {"source_cache": "artifacts/chromium-research/41108476.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7c71767b7a3b58e61b7961f55febf9d637807fe598539f4257a3b1e40fe03fb3", "start_char": 0, "end_char": 1865, "text_sha256": "7c71767b7a3b58e61b7961f55febf9d637807fe598539f4257a3b1e40fe03fb3"} [chromium-p41108476] Chromium Mitigates the Iron-Induced Glucose Metabolism Disorder via the PI3K/Akt/Bcl-2 Signaling Pathway: An In Vivo Study in Wistar Rats. (2026). https://pubmed.ncbi.nlm.nih.gov/41108476/ DOI: 10.1007/s12011-025-04867-9

evidence_span

{"source_cache": "artifacts/chromium-research/41108476.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7c71767b7a3b58e61b7961f55febf9d637807fe598539f4257a3b1e40fe03fb3", "start_char": 0, "end_char": 1865, "text_sha256": "7c71767b7a3b58e61b7961f55febf9d637807fe598539f4257a3b1e40fe03fb3"}

experimental_model

Five-group iron-excess supplementation experiment; 30 rats

exposure

Eight weeks; adequate or excessive iron as iron citrate with three chromium-picolinate dose levels

limitations

Small animal experiment with multiple measured changes. Pathway mediation was proposed, not established by a complete intervention on each signaling node; no human treatment or dietary rescue claim.

nutrient_topic

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

organism

Male Wistar rats

plain_language

A later component of the cell-death pathway was lower.

primary_references

[chromium-p41108476] Chromium Mitigates the Iron-Induced Glucose Metabolism Disorder via the PI3K/Akt/Bcl-2 Signaling Pathway: An In Vivo Study in Wistar Rats. (2026). https://pubmed.ncbi.nlm.nih.gov/41108476/ DOI: 10.1007/s12011-025-04867-9

tissue_or_cell_type

Pancreatic tissue and systemic glucose measures

Chromium: transport, insulin signaling, nutrient interactions and essentiality debate (2026-09-17) · lines 848–859

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Five-group iron-excess supplementation experiment; 30 rats · source_derived_draft · unverified_draft

### chromium-iron-rat-caspase9 Chromium treatment countered the iron-associated increase in pancreatic cleaved caspase-9. Condition category: normal nutrient_topic: Chromium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A later component of the cell-death pathway was lower. organism: Male Wistar rats tissue_or_cell_type: Pancreatic tissue and systemic glucose measures experimental_model: Five-group iron-excess supplementation experiment; 30 rats limitations: Small animal experiment with multiple measured changes. Pathway mediation was proposed, not established by a complete intervention on each signaling node; no human treatment or dietary rescue claim. exposure: Eight weeks; adequate or excessive iron as iron citrate with three chromium-picolinate dose levels evidence_span: {"source_cache": "artifacts/chromium-research/41108476.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7c71767b7a3b58e61b7961f55febf9d637807fe598539f4257a3b1e40fe03fb3", "start_char": 0, "end_char": 1865, "text_sha256": "7c71767b7a3b58e61b7961f55febf9d637807fe598539f4257a3b1e40fe03fb3"} [chromium-p41108476] Chromium Mitigates the Iron-Induced Glucose Metabolism Disorder via the PI3K/Akt/Bcl-2 Signaling Pathway: An In Vivo Study in Wistar Rats. (2026). https://pubmed.ncbi.nlm.nih.gov/41108476/ DOI: 10.1007/s12011-025-04867-9

evidence_span

{"source_cache": "artifacts/chromium-research/29164513.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4d99145cb86f4110fd0087f9162fa057d87b445b9bc6a60c6467bb310f5e300b", "start_char": 0, "end_char": 2450, "text_sha256": "4d99145cb86f4110fd0087f9162fa057d87b445b9bc6a60c6467bb310f5e300b"}

experimental_model

Factorial six-group iron-excess/chromium feeding experiment

exposure

Iron 45 versus 180 mg/kg diet; chromium propionate 1, 50 or 500 mg Cr/kg diet; six animals/group

limitations

High-dose animal study. The direction changed with background iron; do not extrapolate a universal nutrient antagonism or human dose ratio.

nutrient_topic

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

organism

Female Wistar rats

plain_language

The same supplement did not have one fixed effect on kidney iron.

primary_references

[chromium-p29164513] The Combined Effects of Iron Excess in the Diet and Chromium(III) Supplementation on the Iron and Chromium Status in Female Rats. (2018). https://pubmed.ncbi.nlm.nih.gov/29164513/ DOI: 10.1007/s12011-017-1203-z

tissue_or_cell_type

Serum, liver and kidney metals

Chromium: transport, insulin signaling, nutrient interactions and essentiality debate (2026-09-17) · lines 523–534

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Factorial six-group iron-excess/chromium feeding experiment · source_derived_draft · unverified_draft

### chromium-renal-iron-context Chromium supplementation reduced kidney iron with adequate dietary iron, but increasing chromium raised kidney iron when the background diet was iron-excessive. Condition category: normal nutrient_topic: Chromium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The same supplement did not have one fixed effect on kidney iron. organism: Female Wistar rats tissue_or_cell_type: Serum, liver and kidney metals experimental_model: Factorial six-group iron-excess/chromium feeding experiment limitations: High-dose animal study. The direction changed with background iron; do not extrapolate a universal nutrient antagonism or human dose ratio. exposure: Iron 45 versus 180 mg/kg diet; chromium propionate 1, 50 or 500 mg Cr/kg diet; six animals/group evidence_span: {"source_cache": "artifacts/chromium-research/29164513.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4d99145cb86f4110fd0087f9162fa057d87b445b9bc6a60c6467bb310f5e300b", "start_char": 0, "end_char": 2450, "text_sha256": "4d99145cb86f4110fd0087f9162fa057d87b445b9bc6a60c6467bb310f5e300b"} [chromium-p29164513] The Combined Effects of Iron Excess in the Diet and Chromium(III) Supplementation on the Iron and Chromium Status in Female Rats. (2018). https://pubmed.ncbi.nlm.nih.gov/29164513/ DOI: 10.1007/s12011-017-1203-z

evidence_span

{"source_cache": "artifacts/curcumin-research/34371810.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c7dc5d4a48b51f1b27c4cca67fa4d5756197ee3baec9d8c1f2ccccfb5789e3e4", "start_char": 0, "end_char": 2316, "text_sha256": "c7dc5d4a48b51f1b27c4cca67fa4d5756197ee3baec9d8c1f2ccccfb5789e3e4"}

experimental_model

Double-blind randomized acute supplementation trial; 155 healthy participants

exposure

HydroCurc 500 mg with 18 or 65 mg ferrous iron versus matched iron controls

limitations

Serum iron appearance is an indirect absorption-related endpoint, not isotope absorption or long-term iron balance; healthy participants and one formulation.

nutrient_topic

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

organism

Homo sapiens

plain_language

This human experiment did not reproduce a reduction in the measured iron response.

primary_references

[curcumin-p34371810] Acute Administration of Bioavailable Curcumin Alongside Ferrous Sulphate Supplements Does Not Impair Iron Absorption in Healthy Adults in a Randomised Trial. (2021). https://pubmed.ncbi.nlm.nih.gov/34371810/ DOI: 10.3390/nu13072300

tissue_or_cell_type

Serum iron at baseline and 180 minutes

Curcumin: metabolism, signaling and nutrient connections (2026-09-17) · lines 736–747

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind randomized acute supplementation trial; 155 healthy participants · source_derived_draft · unverified_draft

### curcumin-human-iron-null HydroCurc did not impair the acute serum-iron response to either tested ferrous-iron dose. Condition category: normal nutrient_topic: Curcumin research collection; topical membership is not evidence of a direct dietary effect. plain_language: This human experiment did not reproduce a reduction in the measured iron response. organism: Homo sapiens tissue_or_cell_type: Serum iron at baseline and 180 minutes experimental_model: Double-blind randomized acute supplementation trial; 155 healthy participants limitations: Serum iron appearance is an indirect absorption-related endpoint, not isotope absorption or long-term iron balance; healthy participants and one formulation. exposure: HydroCurc 500 mg with 18 or 65 mg ferrous iron versus matched iron controls evidence_span: {"source_cache": "artifacts/curcumin-research/34371810.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c7dc5d4a48b51f1b27c4cca67fa4d5756197ee3baec9d8c1f2ccccfb5789e3e4", "start_char": 0, "end_char": 2316, "text_sha256": "c7dc5d4a48b51f1b27c4cca67fa4d5756197ee3baec9d8c1f2ccccfb5789e3e4"} [curcumin-p34371810] Acute Administration of Bioavailable Curcumin Alongside Ferrous Sulphate Supplements Does Not Impair Iron Absorption in Healthy Adults in a Randomised Trial. (2021). https://pubmed.ncbi.nlm.nih.gov/34371810/ DOI: 10.3390/nu13072300

evidence_span

{"source_cache": "artifacts/curcumin-research/24634837.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3c64f5d7dd7206fa30f155d11ee68a90c72432b6ff1837922ee17ef1e811fec7", "start_char": 0, "end_char": 1451, "text_sha256": "3c64f5d7dd7206fa30f155d11ee68a90c72432b6ff1837922ee17ef1e811fec7"}

experimental_model

Six-month feeding comparison in C57BL/6J mice

exposure

Diet containing 0.2% curcumin versus unsupplemented diet

limitations

Long-term mouse findings cannot be equated with acute human supplementation. Expression changes may be adaptive responses, not direct target binding.

nutrient_topic

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

organism

Mus musculus

plain_language

The mouse liver stored less iron.

primary_references

[curcumin-p24634837] Curcumin may impair iron status when fed to mice for six months. (2014). https://pubmed.ncbi.nlm.nih.gov/24634837/ DOI: 10.1016/j.redox.2014.01.018

tissue_or_cell_type

Liver and spleen

Curcumin: metabolism, signaling and nutrient connections (2026-09-17) · lines 632–643

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Six-month feeding comparison in C57BL/6J mice · source_derived_draft · unverified_draft

### curcumin-liver-iron Liver iron stores were reduced after six months. Condition category: normal nutrient_topic: Curcumin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The mouse liver stored less iron. organism: Mus musculus tissue_or_cell_type: Liver and spleen experimental_model: Six-month feeding comparison in C57BL/6J mice limitations: Long-term mouse findings cannot be equated with acute human supplementation. Expression changes may be adaptive responses, not direct target binding. exposure: Diet containing 0.2% curcumin versus unsupplemented diet evidence_span: {"source_cache": "artifacts/curcumin-research/24634837.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3c64f5d7dd7206fa30f155d11ee68a90c72432b6ff1837922ee17ef1e811fec7", "start_char": 0, "end_char": 1451, "text_sha256": "3c64f5d7dd7206fa30f155d11ee68a90c72432b6ff1837922ee17ef1e811fec7"} [curcumin-p24634837] Curcumin may impair iron status when fed to mice for six months. (2014). https://pubmed.ncbi.nlm.nih.gov/24634837/ DOI: 10.1016/j.redox.2014.01.018

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/curcumin-research/18815282.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "37d4724833996e19b5dedff95a592acbfc5123f22cef97d14656b53a82666aa8", "start_char": 0, "end_char": 1368, "text_sha256": "37d4724833996e19b5dedff95a592acbfc5123f22cef97d14656b53a82666aa8"}

experimental_model

26-week mouse feeding experiment with graded dietary iron and curcumin

exposure

Low-iron background with graded curcumin intake

limitations

Mouse dietary exposure; no universal human anemia prediction. Exact dietary concentrations should be checked in the original methods before translating dose.

nutrient_topic

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

organism

Mus musculus

plain_language

Low iron supply changed the consequences of curcumin exposure.

primary_references

[curcumin-p18815282] Curcumin, a cancer chemopreventive and chemotherapeutic agent, is a biologically active iron chelator. (2009). https://pubmed.ncbi.nlm.nih.gov/18815282/ DOI: 10.1182/blood-2008-05-155952

tissue_or_cell_type

Blood and tissue iron

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Curcumin: metabolism, signaling and nutrient connections (2026-09-17) · lines 606–617

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 26-week mouse feeding experiment with graded dietary iron and curcumin · source_derived_draft · unverified_draft

### curcumin-low-iron-hb On the lowest-iron background, curcumin produced a dose-dependent fall in hemoglobin. Condition category: nutrient_deficiency nutrient_topic: Curcumin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Low iron supply changed the consequences of curcumin exposure. organism: Mus musculus tissue_or_cell_type: Blood and tissue iron experimental_model: 26-week mouse feeding experiment with graded dietary iron and curcumin limitations: Mouse dietary exposure; no universal human anemia prediction. Exact dietary concentrations should be checked in the original methods before translating dose. exposure: Low-iron background with graded curcumin intake evidence_span: {"source_cache": "artifacts/curcumin-research/18815282.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "37d4724833996e19b5dedff95a592acbfc5123f22cef97d14656b53a82666aa8", "start_char": 0, "end_char": 1368, "text_sha256": "37d4724833996e19b5dedff95a592acbfc5123f22cef97d14656b53a82666aa8"} [curcumin-p18815282] Curcumin, a cancer chemopreventive and chemotherapeutic agent, is a biologically active iron chelator. (2009). https://pubmed.ncbi.nlm.nih.gov/18815282/ DOI: 10.1182/blood-2008-05-155952

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/curcumin-research/18815282.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "37d4724833996e19b5dedff95a592acbfc5123f22cef97d14656b53a82666aa8", "start_char": 0, "end_char": 1368, "text_sha256": "37d4724833996e19b5dedff95a592acbfc5123f22cef97d14656b53a82666aa8"}

experimental_model

26-week mouse feeding experiment with graded dietary iron and curcumin

exposure

Low-iron background with graded curcumin intake

limitations

Mouse dietary exposure; no universal human anemia prediction. Exact dietary concentrations should be checked in the original methods before translating dose.

nutrient_topic

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

organism

Mus musculus

plain_language

Less of the blood iron carrier was loaded with iron.

primary_references

[curcumin-p18815282] Curcumin, a cancer chemopreventive and chemotherapeutic agent, is a biologically active iron chelator. (2009). https://pubmed.ncbi.nlm.nih.gov/18815282/ DOI: 10.1182/blood-2008-05-155952

tissue_or_cell_type

Blood and tissue iron

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Curcumin: metabolism, signaling and nutrient connections (2026-09-17) · lines 619–630

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 26-week mouse feeding experiment with graded dietary iron and curcumin · source_derived_draft · unverified_draft

### curcumin-low-iron-tsat Transferrin saturation declined with curcumin on the low-iron background. Condition category: nutrient_deficiency nutrient_topic: Curcumin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Less of the blood iron carrier was loaded with iron. organism: Mus musculus tissue_or_cell_type: Blood and tissue iron experimental_model: 26-week mouse feeding experiment with graded dietary iron and curcumin limitations: Mouse dietary exposure; no universal human anemia prediction. Exact dietary concentrations should be checked in the original methods before translating dose. exposure: Low-iron background with graded curcumin intake evidence_span: {"source_cache": "artifacts/curcumin-research/18815282.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "37d4724833996e19b5dedff95a592acbfc5123f22cef97d14656b53a82666aa8", "start_char": 0, "end_char": 1368, "text_sha256": "37d4724833996e19b5dedff95a592acbfc5123f22cef97d14656b53a82666aa8"} [curcumin-p18815282] Curcumin, a cancer chemopreventive and chemotherapeutic agent, is a biologically active iron chelator. (2009). https://pubmed.ncbi.nlm.nih.gov/18815282/ DOI: 10.1182/blood-2008-05-155952

evidence_span

{"source_cache": "artifacts/curcumin-research/24634837.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3c64f5d7dd7206fa30f155d11ee68a90c72432b6ff1837922ee17ef1e811fec7", "start_char": 0, "end_char": 1451, "text_sha256": "3c64f5d7dd7206fa30f155d11ee68a90c72432b6ff1837922ee17ef1e811fec7"}

experimental_model

Six-month feeding comparison in C57BL/6J mice

exposure

Diet containing 0.2% curcumin versus unsupplemented diet

limitations

Long-term mouse findings cannot be equated with acute human supplementation. Expression changes may be adaptive responses, not direct target binding.

nutrient_topic

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

organism

Mus musculus

plain_language

The storage effect also involved the spleen.

primary_references

[curcumin-p24634837] Curcumin may impair iron status when fed to mice for six months. (2014). https://pubmed.ncbi.nlm.nih.gov/24634837/ DOI: 10.1016/j.redox.2014.01.018

tissue_or_cell_type

Liver and spleen

Curcumin: metabolism, signaling and nutrient connections (2026-09-17) · lines 645–656

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Six-month feeding comparison in C57BL/6J mice · source_derived_draft · unverified_draft

### curcumin-spleen-iron Splenic iron stores were reduced. Condition category: normal nutrient_topic: Curcumin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The storage effect also involved the spleen. organism: Mus musculus tissue_or_cell_type: Liver and spleen experimental_model: Six-month feeding comparison in C57BL/6J mice limitations: Long-term mouse findings cannot be equated with acute human supplementation. Expression changes may be adaptive responses, not direct target binding. exposure: Diet containing 0.2% curcumin versus unsupplemented diet evidence_span: {"source_cache": "artifacts/curcumin-research/24634837.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3c64f5d7dd7206fa30f155d11ee68a90c72432b6ff1837922ee17ef1e811fec7", "start_char": 0, "end_char": 1451, "text_sha256": "3c64f5d7dd7206fa30f155d11ee68a90c72432b6ff1837922ee17ef1e811fec7"} [curcumin-p24634837] Curcumin may impair iron status when fed to mice for six months. (2014). https://pubmed.ncbi.nlm.nih.gov/24634837/ DOI: 10.1016/j.redox.2014.01.018

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

B2 and iron supply can constrain different parts of erythropoiesis.

experimental_model

Controlled supplementation study in riboflavin-deficient Gambian men with hemoglobin below 11.5 g/dL; stable-isotope iron absorption.

exposure

Oral riboflavin versus no riboflavin; 3.38 mg 58Fe test dose before and after intervention; treatment dose not inferred from accessed abstract.

limitations

Controlled study in anemic deficient men; the specific marrow or mobilization mechanism was inferred, not directly established.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Homo sapiens

plain_language

Hemoglobin improved even though the measured storage marker stayed low.

primary_references

[b2-fairweather1992] Riboflavin deficiency and iron absorption in adult Gambian men (1992). https://pubmed.ncbi.nlm.nih.gov/1590670/ DOI: 10.1159/000177696

tissue_or_cell_type

Human clinical setting

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1578–1589

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Controlled supplementation study in riboflavin-deficient Gambian men with hemoglobin below 11.5 g/dL; stable-isotope iron absorption. · source_derived_draft · unverified_draft

### b2-gambia-hemoglobin Riboflavin supplementation improved B2 status and hemoglobin in deficient Gambian men; low plasma ferritin did not change. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Hemoglobin improved even though the measured storage marker stayed low. organism: Homo sapiens tissue_or_cell_type: Human clinical setting experimental_model: Controlled supplementation study in riboflavin-deficient Gambian men with hemoglobin below 11.5 g/dL; stable-isotope iron absorption. limitations: Controlled study in anemic deficient men; the specific marrow or mobilization mechanism was inferred, not directly established. exposure: Oral riboflavin versus no riboflavin; 3.38 mg 58Fe test dose before and after intervention; treatment dose not inferred from accessed abstract. cross_nutrient: B2 and iron supply can constrain different parts of erythropoiesis. [b2-fairweather1992] Riboflavin deficiency and iron absorption in adult Gambian men (1992). https://pubmed.ncbi.nlm.nih.gov/1590670/ DOI: 10.1159/000177696

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Iron-use improvement is distinct from intestinal absorption.

experimental_model

Controlled supplementation study in riboflavin-deficient Gambian men with hemoglobin below 11.5 g/dL; stable-isotope iron absorption.

exposure

Oral riboflavin versus no riboflavin; 3.38 mg 58Fe test dose before and after intervention; treatment dose not inferred from accessed abstract.

limitations

Measurement variability and study size limit exclusion of smaller effects; rat intestinal findings need separate model labels.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Homo sapiens

plain_language

This human study does not support a blanket claim that B2 always raises iron absorption.

primary_references

[b2-fairweather1992] Riboflavin deficiency and iron absorption in adult Gambian men (1992). https://pubmed.ncbi.nlm.nih.gov/1590670/ DOI: 10.1159/000177696

tissue_or_cell_type

Human clinical setting

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1591–1602

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Controlled supplementation study in riboflavin-deficient Gambian men with hemoglobin below 11.5 g/dL; stable-isotope iron absorption. · source_derived_draft · unverified_draft

### b2-gambia-iron-absorption Stable-isotope iron absorption varied widely within and between Gambian participants and showed no measurable change after riboflavin. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: This human study does not support a blanket claim that B2 always raises iron absorption. organism: Homo sapiens tissue_or_cell_type: Human clinical setting experimental_model: Controlled supplementation study in riboflavin-deficient Gambian men with hemoglobin below 11.5 g/dL; stable-isotope iron absorption. limitations: Measurement variability and study size limit exclusion of smaller effects; rat intestinal findings need separate model labels. exposure: Oral riboflavin versus no riboflavin; 3.38 mg 58Fe test dose before and after intervention; treatment dose not inferred from accessed abstract. cross_nutrient: Iron-use improvement is distinct from intestinal absorption. [b2-fairweather1992] Riboflavin deficiency and iron absorption in adult Gambian men (1992). https://pubmed.ncbi.nlm.nih.gov/1590670/ DOI: 10.1159/000177696

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Iron supply alone did not prevent anemia in the combined B2 restriction/antagonist experiment.

experimental_model

Historical induced-depletion study in six men with inoperable cancers; no healthy randomized control group.

exposure

Low-riboflavin semisynthetic diet plus galactoflavin antagonist, followed by riboflavin replacement; three also received oral antibiotics.

limitations

Same six-patient experiment as lesion record; other nutrients were supplied but cancer and antagonist effects limit causal generalization.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Homo sapiens

plain_language

Severe induced shortage reduced new red-cell production; the anemia was not simply assumed to be low dietary iron.

primary_references

[b2-lane1964] THE RAPID INDUCTION OF HUMAN RIBOFLAVIN DEFICIENCY WITH GALACTOFLAVIN (1964). https://pubmed.ncbi.nlm.nih.gov/14135487/ DOI: 10.1172/jci104921

tissue_or_cell_type

Bone marrow and circulating erythrocytes

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1801–1812

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Historical induced-depletion study in six men with inoperable cancers; no healthy randomized control group. · source_derived_draft · unverified_draft

### b2-induced-erythroid-suppression All six patients developed anemia; the study described low reticulocytes and erythroid suppression with recovery during riboflavin replacement. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Severe induced shortage reduced new red-cell production; the anemia was not simply assumed to be low dietary iron. organism: Homo sapiens tissue_or_cell_type: Bone marrow and circulating erythrocytes experimental_model: Historical induced-depletion study in six men with inoperable cancers; no healthy randomized control group. limitations: Same six-patient experiment as lesion record; other nutrients were supplied but cancer and antagonist effects limit causal generalization. exposure: Low-riboflavin semisynthetic diet plus galactoflavin antagonist, followed by riboflavin replacement; three also received oral antibiotics. cross_nutrient: Iron supply alone did not prevent anemia in the combined B2 restriction/antagonist experiment. [b2-lane1964] THE RAPID INDUCTION OF HUMAN RIBOFLAVIN DEFICIENCY WITH GALACTOFLAVIN (1964). https://pubmed.ncbi.nlm.nih.gov/14135487/ DOI: 10.1172/jci104921

cross_nutrient

Direct mechanistic integration of an iron-containing center with B2-derived FAD.

evidence_spans

[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC3106343", "locator": "HTML article p", "paragraph_index": 51, "char_start": 0, "char_end": 1197, "evidence_access": "full-text"}]

experimental_model

Recombinant Rhodobacter sphaeroides ETF-QO; human ETF and MCAD in mixed-species reconstitution; mutagenesis and EPR.

exposure

No nutrient intervention; structural or biochemical characterization.

limitations

Mechanistic inference from mutagenesis/EPR and activity; no dietary iron or B2 intervention.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Rhodobacter sphaeroides; human ETF/MCAD reagents

plain_language

ETF-QO uses its iron-sulfur center and flavin for different stages of the electron relay.

primary_references

[swanson-2008-etf-qo] The iron-sulfur cluster of electron transfer flavoprotein-ubiquinone oxidoreductase is the electron acceptor for electron transfer flavoprotein (2008). https://pubmed.ncbi.nlm.nih.gov/18672901/ DOI: 10.1021/bi800507p

tissue_or_cell_type

Purified proteins

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 794–806

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant Rhodobacter sphaeroides ETF-QO; human ETF and MCAD in mixed-species reconstitution; mutagenesis and EPR. · source_derived_draft · unverified_draft

### b2-met-etf-qo-iron-sulfur-entry Selective effects of ETF-QO FAD-site mutations supported electron entry from ETF through the [4Fe-4S] center, followed by flavin-mediated transfer to ubiquinone. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: ETF-QO uses its iron-sulfur center and flavin for different stages of the electron relay. organism: Rhodobacter sphaeroides; human ETF/MCAD reagents tissue_or_cell_type: Purified proteins experimental_model: Recombinant Rhodobacter sphaeroides ETF-QO; human ETF and MCAD in mixed-species reconstitution; mutagenesis and EPR. limitations: Mechanistic inference from mutagenesis/EPR and activity; no dietary iron or B2 intervention. exposure: No nutrient intervention; structural or biochemical characterization. cross_nutrient: Direct mechanistic integration of an iron-containing center with B2-derived FAD. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC3106343", "locator": "HTML article p", "paragraph_index": 51, "char_start": 0, "char_end": 1197, "evidence_access": "full-text"}] [swanson-2008-etf-qo] The iron-sulfur cluster of electron transfer flavoprotein-ubiquinone oxidoreductase is the electron acceptor for electron transfer flavoprotein (2008). https://pubmed.ncbi.nlm.nih.gov/18672901/ DOI: 10.1021/bi800507p

cross_nutrient

B2-derived FAD and iron-containing redox centers cooperate within one respiratory complex.

evidence_spans

[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC10161127", "locator": "XML .//body//p", "paragraph_index": 2, "char_start": 0, "char_end": 1105, "evidence_access": "full-text"}]

experimental_model

Human complex II purified from HEK293F cells, cryo-EM, EPR and succinate-quinone activity assays.

exposure

No nutrient intervention; structural or biochemical characterization.

limitations

Structural co-dependence does not show that B2 corrects iron deficiency or that iron supplementation improves this reaction.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Homo sapiens

plain_language

Complex II couples a B2-derived flavin with separate iron-sulfur centers.

primary_references

[du-2023-human-complex-ii] Structure of the human respiratory complex II (2023). https://pubmed.ncbi.nlm.nih.gov/37098072/ DOI: 10.1073/pnas.2216713120

tissue_or_cell_type

HEK293F-derived purified complex II

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 649–661

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human complex II purified from HEK293F cells, cryo-EM, EPR and succinate-quinone activity assays. · source_derived_draft · unverified_draft

### b2-met-human-sdhb-iron-sulfur Human complex II structure and EPR resolved SDHB-associated [2Fe-2S], [4Fe-4S] and [3Fe-4S] redox centers adjacent to its SDHA FAD system. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Complex II couples a B2-derived flavin with separate iron-sulfur centers. organism: Homo sapiens tissue_or_cell_type: HEK293F-derived purified complex II experimental_model: Human complex II purified from HEK293F cells, cryo-EM, EPR and succinate-quinone activity assays. limitations: Structural co-dependence does not show that B2 corrects iron deficiency or that iron supplementation improves this reaction. exposure: No nutrient intervention; structural or biochemical characterization. cross_nutrient: B2-derived FAD and iron-containing redox centers cooperate within one respiratory complex. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC10161127", "locator": "XML .//body//p", "paragraph_index": 2, "char_start": 0, "char_end": 1105, "evidence_access": "full-text"}] [du-2023-human-complex-ii] Structure of the human respiratory complex II (2023). https://pubmed.ncbi.nlm.nih.gov/37098072/ DOI: 10.1073/pnas.2216713120

cross_nutrient

B2-derived FAD and iron-containing cluster are distinct required molecular components; this does not establish supplement interactions.

evidence_spans

[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC1637562", "locator": "HTML article p", "paragraph_index": 10, "char_start": 0, "char_end": 3701, "evidence_access": "full-text"}]

experimental_model

Purified porcine ETF-QO crystal structures with and without bound ubiquinone.

exposure

No nutrient intervention; structural or biochemical characterization.

limitations

Static structure; the exact electron-entry sequence required additional functional experiments.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Sus scrofa

plain_language

ETF-QO combines flavin and iron-sulfur chemistry in one protein downstream of ETF.

primary_references

[zhang-2006-etf-qo] Structure of electron transfer flavoprotein-ubiquinone oxidoreductase and electron transfer to the mitochondrial ubiquinone pool (2006). https://pubmed.ncbi.nlm.nih.gov/17050691/ DOI: 10.1073/pnas.0604567103

tissue_or_cell_type

Purified porcine mitochondrial ETF-QO

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 767–779

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified porcine ETF-QO crystal structures with and without bound ubiquinone. · source_derived_draft · unverified_draft

### b2-met-porcine-etfdh-cofactors Porcine ETF-QO crystal structures resolved one FAD and one [4Fe-4S] cluster per protein, together with a separate ubiquinone-binding region. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: ETF-QO combines flavin and iron-sulfur chemistry in one protein downstream of ETF. organism: Sus scrofa tissue_or_cell_type: Purified porcine mitochondrial ETF-QO experimental_model: Purified porcine ETF-QO crystal structures with and without bound ubiquinone. limitations: Static structure; the exact electron-entry sequence required additional functional experiments. exposure: No nutrient intervention; structural or biochemical characterization. cross_nutrient: B2-derived FAD and iron-containing cluster are distinct required molecular components; this does not establish supplement interactions. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC1637562", "locator": "HTML article p", "paragraph_index": 10, "char_start": 0, "char_end": 3701, "evidence_access": "full-text"}] [zhang-2006-etf-qo] Structure of electron transfer flavoprotein-ubiquinone oxidoreductase and electron transfer to the mitochondrial ubiquinone pool (2006). https://pubmed.ncbi.nlm.nih.gov/17050691/ DOI: 10.1073/pnas.0604567103

cross_nutrient

Direct clinical comparison involving B2, vitamin A, iron and folic acid.

experimental_model

366 anemic pregnant women in rural China randomized among four groups for two months; all received iron and folic acid.

exposure

All arms: 60 mg/day iron plus 400 micrograms/day folic acid; added retinol 2000 micrograms/day, riboflavin 1 mg/day, both, or neither. Trial exposures, not recommendations.

limitations

Combination effect cannot be assigned solely to B2 or assumed to be biochemical synergy; anemic pregnant population, multiple co-deficiencies, two-month endpoint.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Homo sapiens

plain_language

Several nutrients were limiting in this population; the combination helped more than iron and folic acid alone.

primary_references

[b2-ma2008] Retinol and riboflavin supplementation decreases the prevalence of anemia in Chinese pregnant women taking iron and folic Acid supplements (2008). https://pubmed.ncbi.nlm.nih.gov/18806105/ DOI: 10.1093/jn/138.10.1946

tissue_or_cell_type

Human clinical setting

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1604–1615

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 366 anemic pregnant women in rural China randomized among four groups for two months; all received iron and folic acid. · source_derived_draft · unverified_draft

### b2-pregnancy-multiple-nutrients Adding retinol and/or riboflavin to iron-folic-acid treatment reduced anemia prevalence more than iron-folic-acid alone; the combined retinol-riboflavin arm gained 5.4±1.1 g/L more hemoglobin than the reference arm. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Several nutrients were limiting in this population; the combination helped more than iron and folic acid alone. organism: Homo sapiens tissue_or_cell_type: Human clinical setting experimental_model: 366 anemic pregnant women in rural China randomized among four groups for two months; all received iron and folic acid. limitations: Combination effect cannot be assigned solely to B2 or assumed to be biochemical synergy; anemic pregnant population, multiple co-deficiencies, two-month endpoint. exposure: All arms: 60 mg/day iron plus 400 micrograms/day folic acid; added retinol 2000 micrograms/day, riboflavin 1 mg/day, both, or neither. Trial exposures, not recommendations. cross_nutrient: Direct clinical comparison involving B2, vitamin A, iron and folic acid. [b2-ma2008] Retinol and riboflavin supplementation decreases the prevalence of anemia in Chinese pregnant women taking iron and folic Acid supplements (2008). https://pubmed.ncbi.nlm.nih.gov/18806105/ DOI: 10.1093/jn/138.10.1946

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

B2 status affected post-absorption iron retention in rats.

evidence_location

Abstract

experimental_model

Riboflavin-deficient weanling rats; weight-matched and ad-libitum controls; intestinal histology and intraperitoneal 59Fe tracing.

exposure

Dietary riboflavin deficiency plus intraperitoneal tracer

limitations

The proposed enterocyte-turnover mechanism is supported indirectly; this is not measurement of unabsorbed oral iron.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Rattus norvegicus

plain_language

Deficiency increased loss of iron already inside the body.

primary_references

[powers1993] A proposed intestinal mechanism for the effect of riboflavin deficiency on iron loss in the rat. (1993). https://pubmed.ncbi.nlm.nih.gov/8490008/ DOI: 10.1079/bjn19930055

tissue_or_cell_type

Gastrointestinal tract and feces

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1458–1470

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Riboflavin-deficient weanling rats; weight-matched and ad-libitum controls; intestinal histology and intraperitoneal 59Fe tracing. · source_derived_draft · unverified_draft

### b2-rat-endogenous-iron-loss After intraperitoneal 59Fe, riboflavin-deficient rats lost about twice as much endogenous tracer in feces as weight-matched controls. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Deficiency increased loss of iron already inside the body. organism: Rattus norvegicus tissue_or_cell_type: Gastrointestinal tract and feces experimental_model: Riboflavin-deficient weanling rats; weight-matched and ad-libitum controls; intestinal histology and intraperitoneal 59Fe tracing. limitations: The proposed enterocyte-turnover mechanism is supported indirectly; this is not measurement of unabsorbed oral iron. exposure: Dietary riboflavin deficiency plus intraperitoneal tracer cross_nutrient: B2 status affected post-absorption iron retention in rats. evidence_location: Abstract [powers1993] A proposed intestinal mechanism for the effect of riboflavin deficiency on iron loss in the rat. (1993). https://pubmed.ncbi.nlm.nih.gov/8490008/ DOI: 10.1079/bjn19930055

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

B2 status changed systemic appearance of administered iron.

evidence_location

Abstract

experimental_model

Dietary riboflavin-deficient male rats versus age-/weight-matched controls; intragastric 59Fe and mucosal brush-border vesicles.

exposure

Dietary riboflavin deficiency plus intragastric 59Fe

limitations

Rat tracer experiment; does not establish an identical human absorption response.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Rattus norvegicus

plain_language

Less of the administered iron reached the blood.

primary_references

[butler1993] Comparison of changes in the uptake and mucosal processing of iron in riboflavin-deficient rats. (1993). https://pubmed.ncbi.nlm.nih.gov/8358336/

tissue_or_cell_type

Intestine and plasma

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1416–1428

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dietary riboflavin-deficient male rats versus age-/weight-matched controls; intragastric 59Fe and mucosal brush-border vesicles. · source_derived_draft · unverified_draft

### b2-rat-enteral-iron-transfer Riboflavin-deficient rats transferred less intragastrically administered 59Fe to plasma than age- or weight-matched controls. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Less of the administered iron reached the blood. organism: Rattus norvegicus tissue_or_cell_type: Intestine and plasma experimental_model: Dietary riboflavin-deficient male rats versus age-/weight-matched controls; intragastric 59Fe and mucosal brush-border vesicles. limitations: Rat tracer experiment; does not establish an identical human absorption response. exposure: Dietary riboflavin deficiency plus intragastric 59Fe cross_nutrient: B2 status changed systemic appearance of administered iron. evidence_location: Abstract [butler1993] Comparison of changes in the uptake and mucosal processing of iron in riboflavin-deficient rats. (1993). https://pubmed.ncbi.nlm.nih.gov/8358336/

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

B2 deficiency impairs an iron-uptake process in this rat model.

evidence_location

Abstract

experimental_model

Dietary riboflavin-deficient male rats versus age-/weight-matched controls; intragastric 59Fe and mucosal brush-border vesicles.

exposure

Dietary riboflavin deficiency

limitations

No specific transporter or ferrireductase was identified; the result must not be assigned to DMT1, DCYTB or ferritin release without evidence.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Rattus norvegicus

plain_language

The deficiency affected iron entry at the intestinal surface.

primary_references

[butler1993] Comparison of changes in the uptake and mucosal processing of iron in riboflavin-deficient rats. (1993). https://pubmed.ncbi.nlm.nih.gov/8358336/

tissue_or_cell_type

Intestinal brush-border membrane vesicles

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1402–1414

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dietary riboflavin-deficient male rats versus age-/weight-matched controls; intragastric 59Fe and mucosal brush-border vesicles. · source_derived_draft · unverified_draft

### b2-rat-iron-brush-border-uptake Brush-border membrane vesicles from riboflavin-deficient rats took up less iron than identically prepared control vesicles. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The deficiency affected iron entry at the intestinal surface. organism: Rattus norvegicus tissue_or_cell_type: Intestinal brush-border membrane vesicles experimental_model: Dietary riboflavin-deficient male rats versus age-/weight-matched controls; intragastric 59Fe and mucosal brush-border vesicles. limitations: No specific transporter or ferrireductase was identified; the result must not be assigned to DMT1, DCYTB or ferritin release without evidence. exposure: Dietary riboflavin deficiency cross_nutrient: B2 deficiency impairs an iron-uptake process in this rat model. evidence_location: Abstract [butler1993] Comparison of changes in the uptake and mucosal processing of iron in riboflavin-deficient rats. (1993). https://pubmed.ncbi.nlm.nih.gov/8358336/

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Constrains the proposed B2-iron mechanism.

evidence_location

Abstract

experimental_model

Dietary riboflavin-deficient male rats versus age-/weight-matched controls; intragastric 59Fe and mucosal brush-border vesicles.

exposure

Dietary riboflavin deficiency; 30-minute tracer endpoint

limitations

Only the reported pools and time point were compared.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Rattus norvegicus

plain_language

The uptake decrease was not explained by the tested redistribution hypothesis.

primary_references

[butler1993] Comparison of changes in the uptake and mucosal processing of iron in riboflavin-deficient rats. (1993). https://pubmed.ncbi.nlm.nih.gov/8358336/

tissue_or_cell_type

Intestinal mucosa

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1430–1442

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dietary riboflavin-deficient male rats versus age-/weight-matched controls; intragastric 59Fe and mucosal brush-border vesicles. · source_derived_draft · unverified_draft

### b2-rat-iron-partition-preserved Thirty minutes after iron dosing, riboflavin-deficient rats had less mucosal 59Fe but unchanged relative partition between ferritin and transferrin. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The uptake decrease was not explained by the tested redistribution hypothesis. organism: Rattus norvegicus tissue_or_cell_type: Intestinal mucosa experimental_model: Dietary riboflavin-deficient male rats versus age-/weight-matched controls; intragastric 59Fe and mucosal brush-border vesicles. limitations: Only the reported pools and time point were compared. exposure: Dietary riboflavin deficiency; 30-minute tracer endpoint cross_nutrient: Constrains the proposed B2-iron mechanism. evidence_location: Abstract [butler1993] Comparison of changes in the uptake and mucosal processing of iron in riboflavin-deficient rats. (1993). https://pubmed.ncbi.nlm.nih.gov/8358336/

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Iron absorption and iron use remain separate entities.

experimental_model

RIBOFEM: 123 UK women aged 19-25 randomized with EGRAC >1.40; 119 completed, 117 analyzed after two exclusions; iron-absorption subset 34.

exposure

Placebo, 2 or 4 mg/day riboflavin for eight weeks; historical trial regimens.

limitations

Small absorption subgroup; no measured change is not proof of identical absorption in all settings. Actual downstream causal step remains unresolved.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Homo sapiens

plain_language

The blood response could not simply be explained by absorbing more iron in the measured subgroup.

primary_references

[b2-powers2011] Correcting a marginal riboflavin deficiency improves hematologic status in young women in the United Kingdom (RIBOFEM) (2011). https://pubmed.ncbi.nlm.nih.gov/21525198/ DOI: 10.3945/ajcn.110.008409

tissue_or_cell_type

Human clinical setting

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1565–1576

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · RIBOFEM: 123 UK women aged 19-25 randomized with EGRAC >1.40; 119 completed, 117 analyzed after two exclusions; iron-absorption subset 34. · source_derived_draft · unverified_draft

### b2-ribofem-absorption RIBOFEM found no change in dietary iron intake or measured iron absorption during the riboflavin intervention. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The blood response could not simply be explained by absorbing more iron in the measured subgroup. organism: Homo sapiens tissue_or_cell_type: Human clinical setting experimental_model: RIBOFEM: 123 UK women aged 19-25 randomized with EGRAC >1.40; 119 completed, 117 analyzed after two exclusions; iron-absorption subset 34. limitations: Small absorption subgroup; no measured change is not proof of identical absorption in all settings. Actual downstream causal step remains unresolved. exposure: Placebo, 2 or 4 mg/day riboflavin for eight weeks; historical trial regimens. cross_nutrient: Iron absorption and iron use remain separate entities. [b2-powers2011] Correcting a marginal riboflavin deficiency improves hematologic status in young women in the United Kingdom (RIBOFEM) (2011). https://pubmed.ncbi.nlm.nih.gov/21525198/ DOI: 10.3945/ajcn.110.008409

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Riboflavin status modifies iron-related hematologic outcomes.

experimental_model

RIBOFEM: 123 UK women aged 19-25 randomized with EGRAC >1.40; 119 completed, 117 analyzed after two exclusions; iron-absorption subset 34.

exposure

Placebo, 2 or 4 mg/day riboflavin for eight weeks; historical trial regimens.

limitations

Baseline-tertile and response associations should not be restated as a uniform hemoglobin benefit in every randomized participant.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Homo sapiens

plain_language

Women with poorer starting B2 status tended to gain more hemoglobin when their B2 status improved.

primary_references

[b2-powers2011] Correcting a marginal riboflavin deficiency improves hematologic status in young women in the United Kingdom (RIBOFEM) (2011). https://pubmed.ncbi.nlm.nih.gov/21525198/ DOI: 10.3945/ajcn.110.008409

tissue_or_cell_type

Human clinical setting

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1552–1563

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · RIBOFEM: 123 UK women aged 19-25 randomized with EGRAC >1.40; 119 completed, 117 analyzed after two exclusions; iron-absorption subset 34. · source_derived_draft · unverified_draft

### b2-ribofem-hemoglobin In RIBOFEM, improvement in B2 status correlated with hemoglobin increase among supplemented women; women with baseline EGRAC >1.65 had the greater hemoglobin response. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Women with poorer starting B2 status tended to gain more hemoglobin when their B2 status improved. organism: Homo sapiens tissue_or_cell_type: Human clinical setting experimental_model: RIBOFEM: 123 UK women aged 19-25 randomized with EGRAC >1.40; 119 completed, 117 analyzed after two exclusions; iron-absorption subset 34. limitations: Baseline-tertile and response associations should not be restated as a uniform hemoglobin benefit in every randomized participant. exposure: Placebo, 2 or 4 mg/day riboflavin for eight weeks; historical trial regimens. cross_nutrient: Riboflavin status modifies iron-related hematologic outcomes. [b2-powers2011] Correcting a marginal riboflavin deficiency improves hematologic status in young women in the United Kingdom (RIBOFEM) (2011). https://pubmed.ncbi.nlm.nih.gov/21525198/ DOI: 10.3945/ajcn.110.008409

evidence_access

Primary abstract

experimental_model

Human apo and iron-bound HGD crystallography.

limitations

The study is structural/enzymatic evidence, not a trial of iron supplementation.

nutrient_topic

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

plain_language

Iron-dependent chemistry opens the aromatic ring for further breakdown.

primary_references

Crystal structure of human homogentisate dioxygenase. · 2000 · https://pubmed.ncbi.nlm.nih.gov/10876237/ · DOI 10.1038/76756

L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 236–242

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human apo and iron-bound HGD crystallography. · source_derived_draft · unverified_draft

## l-tyrosine-hgd-ring Iron-dependent chemistry opens the aromatic ring for further breakdown. Human HGD catalyzes aromatic-ring cleavage during phenylalanine/tyrosine degradation; its structure contains a coordinated active-site iron ion. Model: Human apo and iron-bound HGD crystallography. Limitations: The study is structural/enzymatic evidence, not a trial of iron supplementation. Evidence access: Primary abstract Crystal structure of human homogentisate dioxygenase. · 2000 · https://pubmed.ncbi.nlm.nih.gov/10876237/ · DOI 10.1038/76756

evidence_access

Primary abstract

experimental_model

Human enzyme mutagenesis, binding assays and structural simulation.

limitations

HPD must not be merged with HPDL, which has a different product.

nutrient_topic

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

plain_language

The carbon skeleton passes through a separate oxygen-dependent enzyme.

primary_references

Functional role of residues involved in substrate binding of human 4-hydroxyphenylpyruvate dioxygenase. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34047349/ · DOI 10.1042/BCJ20210005

L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 228–234

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

## l-tyrosine-hpd-hga The carbon skeleton passes through a separate oxygen-dependent enzyme. Human HPD converts 4-hydroxyphenylpyruvate to homogentisate; substrate-binding-site mutations altered catalytic efficiency. Model: Human enzyme mutagenesis, binding assays and structural simulation. Limitations: HPD must not be merged with HPDL, which has a different product. Evidence access: Primary abstract Functional role of residues involved in substrate binding of human 4-hydroxyphenylpyruvate dioxygenase. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34047349/ · DOI 10.1042/BCJ20210005

access_level

selected_indexed_full_text_passages

evidence_cache

artifacts/discovery-research/round2-sources/primary-mechanism-passages.json; SHA256 81c0207494f0b2a22fd0af0d70528a5114dfd74367dd99f967f4ada68c53e8c3

experimental_model

Human cultured cells

exposure

Pharmacological DFO; panel-specific dose/time unresolved

limitations

Selected indexed primary full-text passages reviewed; supplements not independently inspected in this round. These records do not demonstrate iron-chelation rescue of SLC25A39 loss, clinical benefit, or transfer to pulmonary endothelium.

organism

Human cultured cells; mouse xenograft host only for colonization endpoint

plain_language

Iron chelation arrested DELE1 import and stabilized full-length DELE1 at the mitochondrial surface.

primary_locator

https://pmc.ncbi.nlm.nih.gov/articles/PMC10329284/ Results: DELE1 on mitochondrial surface activates HRI; Figures 5–6

primary_references

https://doi.org/10.1016/j.molcel.2023.05.031

DELE1 bridge: iron sensing and mitochondrial-glutathione-dependent stress signaling · lines 55–64

Targeted primary-literature curation; selected indexed full-text passages, 2026-09-20. · supports · Human cultured cells · source_derived_draft · unverified_draft

Iron chelation arrested DELE1 import and stabilized full-length DELE1 at the mitochondrial surface. primary_references: https://doi.org/10.1016/j.molcel.2023.05.031 primary_locator: https://pmc.ncbi.nlm.nih.gov/articles/PMC10329284/ Results: DELE1 on mitochondrial surface activates HRI; Figures 5–6 evidence_cache: artifacts/discovery-research/round2-sources/primary-mechanism-passages.json; SHA256 81c0207494f0b2a22fd0af0d70528a5114dfd74367dd99f967f4ada68c53e8c3 access_level: selected_indexed_full_text_passages experimental_model: Human cultured cells organism: Human cultured cells; mouse xenograft host only for colonization endpoint exposure: Pharmacological DFO; panel-specific dose/time unresolved limitations: Selected indexed primary full-text passages reviewed; supplements not independently inspected in this round. These records do not demonstrate iron-chelation rescue of SLC25A39 loss, clinical benefit, or transfer to pulmonary endothelium. plain_language: Iron chelation arrested DELE1 import and stabilized full-length DELE1 at the mitochondrial surface.

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

false

evidence_span

{"source_cache": "artifacts/zinc-transport-sources/22737083-abstract.txt", "locator": "Primary indexed abstract; tissue elemental analysis", "file_sha256": "4643d3986c556a001c45365febbb07095bcdc8bc604e30488d3fb98a23511a4b"}

experimental_model

Tamoxifen-inducible enterocyte-specific knockout and tissue elemental analysis

exposure

Conditional gene deletion compared with intact controls.

limitations

A genetic transport defect is not interchangeable with low intake. Total tissue zinc does not resolve labile versus protein-bound zinc. Tissue accumulation is not proof of systemic nutritional adequacy of the other metals.

nutrient_topic

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

organism

Mus musculus

plain_language

Loss of zinc uptake disrupted the distribution of several other metals.

primary_references

[zinc-trans-22737083] A mouse model of acrodermatitis enteropathica: loss of intestine zinc transporter ZIP4 (Slc39a4) disrupts the stem cell niche and intestine integrity. (2012). https://pubmed.ncbi.nlm.nih.gov/22737083/ DOI: 10.1371/journal.pgen.1002766

tissue_or_cell_type

Small intestine, liver, pancreas

trigger_kind

machinery_impairment Imported condition classification; unverified.

Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 585–597

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Tamoxifen-inducible enterocyte-specific knockout and tissue elemental analysis · source_derived_draft · unverified_draft

### zinc-trans-zip4-other-metals After enterocyte Zip4 deletion in mice, liver iron, manganese and copper gradually accumulated as the zinc-depletion disease progressed. Condition category: machinery_impairment nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Loss of zinc uptake disrupted the distribution of several other metals. organism: Mus musculus tissue_or_cell_type: Small intestine, liver, pancreas experimental_model: Tamoxifen-inducible enterocyte-specific knockout and tissue elemental analysis limitations: A genetic transport defect is not interchangeable with low intake. Total tissue zinc does not resolve labile versus protein-bound zinc. Tissue accumulation is not proof of systemic nutritional adequacy of the other metals. exposure: Conditional gene deletion compared with intact controls. cross_nutrient: false evidence_span: {"source_cache": "artifacts/zinc-transport-sources/22737083-abstract.txt", "locator": "Primary indexed abstract; tissue elemental analysis", "file_sha256": "4643d3986c556a001c45365febbb07095bcdc8bc604e30488d3fb98a23511a4b"} [zinc-trans-22737083] A mouse model of acrodermatitis enteropathica: loss of intestine zinc transporter ZIP4 (Slc39a4) disrupts the stem cell niche and intestine integrity. (2012). https://pubmed.ncbi.nlm.nih.gov/22737083/ DOI: 10.1371/journal.pgen.1002766

cross_nutrient

Copper (affected_nutrient); Iron (coadministered_nutrient); Zinc(II) ion (administered_element)

evidence_location

Indexed primary abstract.

evidence_span

{"source_cache": "artifacts/zinc-clinical-sources/yadrick1989.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "e2d70d43dded75edb026cac237f238d9e59399db6094098796e169f20e819443", "utf8_bytes": 969}

experimental_model

Ten-week zinc or zinc-plus-iron intervention in adult women

exposure

50 mg elemental zinc/day as gluconate, with or without 50 mg iron/day as ferrous sulfate monohydrate.

limitations

Reported comparisons are within-group pretreatment versus 10 weeks, not placebo-adjusted effects. ESOD is a functional biomarker, not a diagnosis of symptomatic copper deficiency.

nutrient_topic

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

organism

Homo sapiens

plain_language

Adding iron did not prevent the fall in this copper/zinc enzyme marker.

primary_references

[zn-clin-yadrick1989] Iron, copper, and zinc status: response to supplementation with zinc or zinc and iron in adult females. (1989). https://pubmed.ncbi.nlm.nih.gov/2912000/ DOI: 10.1093/ajcn/49.1.145

tissue_or_cell_type

Blood and erythrocytes

Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 1181–1194

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ten-week zinc or zinc-plus-iron intervention in adult women · source_derived_draft · unverified_draft

### zn-clin-esod-zinc After ten weeks, erythrocyte Cu/Zn-superoxide dismutase activity was lower than pretreatment in both the zinc-only and zinc-plus-iron groups (P<0.05). Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Adding iron did not prevent the fall in this copper/zinc enzyme marker. organism: Homo sapiens tissue_or_cell_type: Blood and erythrocytes experimental_model: Ten-week zinc or zinc-plus-iron intervention in adult women limitations: Reported comparisons are within-group pretreatment versus 10 weeks, not placebo-adjusted effects. ESOD is a functional biomarker, not a diagnosis of symptomatic copper deficiency. exposure: 50 mg elemental zinc/day as gluconate, with or without 50 mg iron/day as ferrous sulfate monohydrate. cross_nutrient: Copper (affected_nutrient); Iron (coadministered_nutrient); Zinc(II) ion (administered_element) evidence_location: Indexed primary abstract. evidence_span: {"source_cache": "artifacts/zinc-clinical-sources/yadrick1989.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "e2d70d43dded75edb026cac237f238d9e59399db6094098796e169f20e819443", "utf8_bytes": 969} [zn-clin-yadrick1989] Iron, copper, and zinc status: response to supplementation with zinc or zinc and iron in adult females. (1989). https://pubmed.ncbi.nlm.nih.gov/2912000/ DOI: 10.1093/ajcn/49.1.145

cross_nutrient

Zinc(II) ion (absorbed_nutrient_ion); Iron (coadministered_nutrient); L-Ascorbate (coadministered_ligand)

evidence_location

Indexed primary abstract.

evidence_span

{"source_cache": "artifacts/zinc-clinical-sources/sandstrom1985.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "aa462f6a961ec4190690f8def1be1f5e54491574698b131992161a989103ca76", "utf8_bytes": 1044}

experimental_model

Human 65Zn tracer study with whole-body counting after two weeks

exposure

Ferrous iron with ascorbic acid; Fe:Zn molar ratios 1:1, 2.5:1 and 25:1, in fasting water or a meal; histidine and iron-preloading comparisons.

limitations

Meal matrix, iron ratio and ligand differed. Absolute administered amounts and sample sizes were not verified in the indexed abstract; no universal spacing rule follows.

nutrient_topic

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

organism

Homo sapiens

plain_language

The high iron-to-zinc ratio reduced zinc uptake in the fasting solution.

primary_references

[zn-clin-sandstrom1985] Oral iron, dietary ligands and zinc absorption. (1985). https://pubmed.ncbi.nlm.nih.gov/3973750/ DOI: 10.1093/jn/115.3.411

tissue_or_cell_type

Intestinal absorption

Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 1226–1239

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human 65Zn tracer study with whole-body counting after two weeks · source_derived_draft · unverified_draft

### zn-clin-iron-fasting Fasting-water zinc absorption was 59%, 58% and 34% at ferrous Fe:Zn molar ratios of 1:1, 2.5:1 and 25:1 respectively; inhibition was significant at the highest ratio. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: The high iron-to-zinc ratio reduced zinc uptake in the fasting solution. organism: Homo sapiens tissue_or_cell_type: Intestinal absorption experimental_model: Human 65Zn tracer study with whole-body counting after two weeks limitations: Meal matrix, iron ratio and ligand differed. Absolute administered amounts and sample sizes were not verified in the indexed abstract; no universal spacing rule follows. exposure: Ferrous iron with ascorbic acid; Fe:Zn molar ratios 1:1, 2.5:1 and 25:1, in fasting water or a meal; histidine and iron-preloading comparisons. cross_nutrient: Zinc(II) ion (absorbed_nutrient_ion); Iron (coadministered_nutrient); L-Ascorbate (coadministered_ligand) evidence_location: Indexed primary abstract. evidence_span: {"source_cache": "artifacts/zinc-clinical-sources/sandstrom1985.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "aa462f6a961ec4190690f8def1be1f5e54491574698b131992161a989103ca76", "utf8_bytes": 1044} [zn-clin-sandstrom1985] Oral iron, dietary ligands and zinc absorption. (1985). https://pubmed.ncbi.nlm.nih.gov/3973750/ DOI: 10.1093/jn/115.3.411

cross_nutrient

Iron (coadministered_nutrient); Hematocrit (measured_endpoint); Blood hemoglobin concentration (unchanged_endpoint)

evidence_location

Indexed primary abstract.

evidence_span

{"source_cache": "artifacts/zinc-clinical-sources/yadrick1989.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "e2d70d43dded75edb026cac237f238d9e59399db6094098796e169f20e819443", "utf8_bytes": 969}

experimental_model

Ten-week zinc or zinc-plus-iron intervention in adult women

exposure

50 mg elemental zinc/day as gluconate, with or without 50 mg iron/day as ferrous sulfate monohydrate.

limitations

Reported comparisons are within-group pretreatment versus 10 weeks, not placebo-adjusted effects. ESOD is a functional biomarker, not a diagnosis of symptomatic copper deficiency.

nutrient_topic

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

organism

Homo sapiens

plain_language

Iron-status markers responded differently depending on whether iron accompanied zinc.

primary_references

[zn-clin-yadrick1989] Iron, copper, and zinc status: response to supplementation with zinc or zinc and iron in adult females. (1989). https://pubmed.ncbi.nlm.nih.gov/2912000/ DOI: 10.1093/ajcn/49.1.145

tissue_or_cell_type

Blood and erythrocytes

Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 1196–1209

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ten-week zinc or zinc-plus-iron intervention in adult women · source_derived_draft · unverified_draft

### zn-clin-iron-markers Zinc-only treatment was followed by lower serum ferritin and hematocrit; with added iron, ferritin increased and hematocrit was unchanged. Hemoglobin did not change in either group. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Iron-status markers responded differently depending on whether iron accompanied zinc. organism: Homo sapiens tissue_or_cell_type: Blood and erythrocytes experimental_model: Ten-week zinc or zinc-plus-iron intervention in adult women limitations: Reported comparisons are within-group pretreatment versus 10 weeks, not placebo-adjusted effects. ESOD is a functional biomarker, not a diagnosis of symptomatic copper deficiency. exposure: 50 mg elemental zinc/day as gluconate, with or without 50 mg iron/day as ferrous sulfate monohydrate. cross_nutrient: Iron (coadministered_nutrient); Hematocrit (measured_endpoint); Blood hemoglobin concentration (unchanged_endpoint) evidence_location: Indexed primary abstract. evidence_span: {"source_cache": "artifacts/zinc-clinical-sources/yadrick1989.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "e2d70d43dded75edb026cac237f238d9e59399db6094098796e169f20e819443", "utf8_bytes": 969} [zn-clin-yadrick1989] Iron, copper, and zinc status: response to supplementation with zinc or zinc and iron in adult females. (1989). https://pubmed.ncbi.nlm.nih.gov/2912000/ DOI: 10.1093/ajcn/49.1.145

cross_nutrient

Zinc(II) ion (absorbed_nutrient_ion); Iron (dietary_context)

evidence_location

Indexed primary abstract.

evidence_span

{"source_cache": "artifacts/zinc-clinical-sources/sandstrom1985.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "aa462f6a961ec4190690f8def1be1f5e54491574698b131992161a989103ca76", "utf8_bytes": 1044}

experimental_model

Human 65Zn tracer study with whole-body counting after two weeks

exposure

Ferrous iron with ascorbic acid; Fe:Zn molar ratios 1:1, 2.5:1 and 25:1, in fasting water or a meal; histidine and iron-preloading comparisons.

limitations

Meal matrix, iron ratio and ligand differed. Absolute administered amounts and sample sizes were not verified in the indexed abstract; no universal spacing rule follows.

nutrient_topic

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

organism

Homo sapiens

plain_language

The fasting-solution result did not carry over to the tested meal.

primary_references

[zn-clin-sandstrom1985] Oral iron, dietary ligands and zinc absorption. (1985). https://pubmed.ncbi.nlm.nih.gov/3973750/ DOI: 10.1093/jn/115.3.411

tissue_or_cell_type

Intestinal absorption

Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 1241–1254

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human 65Zn tracer study with whole-body counting after two weeks · source_derived_draft · unverified_draft

### zn-clin-iron-meal When the corresponding iron-to-zinc ratios were administered with a meal, zinc absorption was 25%, 23% and 22%, without the inhibitory iron effect detected in fasting water. Two weeks of iron preloading also did not alter zinc absorption from water. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: The fasting-solution result did not carry over to the tested meal. organism: Homo sapiens tissue_or_cell_type: Intestinal absorption experimental_model: Human 65Zn tracer study with whole-body counting after two weeks limitations: Meal matrix, iron ratio and ligand differed. Absolute administered amounts and sample sizes were not verified in the indexed abstract; no universal spacing rule follows. exposure: Ferrous iron with ascorbic acid; Fe:Zn molar ratios 1:1, 2.5:1 and 25:1, in fasting water or a meal; histidine and iron-preloading comparisons. cross_nutrient: Zinc(II) ion (absorbed_nutrient_ion); Iron (dietary_context) evidence_location: Indexed primary abstract. evidence_span: {"source_cache": "artifacts/zinc-clinical-sources/sandstrom1985.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "aa462f6a961ec4190690f8def1be1f5e54491574698b131992161a989103ca76", "utf8_bytes": 1044} [zn-clin-sandstrom1985] Oral iron, dietary ligands and zinc absorption. (1985). https://pubmed.ncbi.nlm.nih.gov/3973750/ DOI: 10.1093/jn/115.3.411

evidence_access

Primary abstract

experimental_model

Human respiratory epithelial-cell exposure to Suwannee River/Nordic reference fulvic fractions; comparison with smoke water-soluble fractions.

limitations

Abstract access; exposure concentration and duration require full-method verification. Increased iron import is consistent with compensatory iron stress, not direct quantification of every intracellular available-iron pool. These are airway-cell exposures, not an oral trial.

nutrient_topic

Fulvic acid collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Fulvic acid (heterogeneous humic fraction)

plain_language

Cells changed their iron handling after direct exposure.

primary_references

A Fulvic Acid-like Substance Participates in the Pro-inflammatory Effects of Cigarette Smoke and Wood Smoke Particles. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32191033/ · DOI 10.1021/acs.chemrestox.0c00036

Fulvic acid: mixture identity, mineral chemistry, signaling and cross-nutrient mechanisms (2026-09-19) · lines 212–218

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human respiratory epithelial-cell exposure to Suwannee River/Nordic reference fulvic fractions; comparison with smoke water-soluble fractions. · source_derived_draft · unverified_draft

## fulvic-acid-airway-iron-import Cells changed their iron handling after direct exposure. Reference fulvic fractions increased iron import in respiratory epithelial cells. Model: Human respiratory epithelial-cell exposure to Suwannee River/Nordic reference fulvic fractions; comparison with smoke water-soluble fractions. Limitations: Abstract access; exposure concentration and duration require full-method verification. Increased iron import is consistent with compensatory iron stress, not direct quantification of every intracellular available-iron pool. These are airway-cell exposures, not an oral trial. Evidence access: Primary abstract A Fulvic Acid-like Substance Participates in the Pro-inflammatory Effects of Cigarette Smoke and Wood Smoke Particles. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32191033/ · DOI 10.1021/acs.chemrestox.0c00036

evidence_access

Primary abstract

experimental_model

Cell-free EXAFS spectroscopy; acidic aqueous solutions at pH 2 and 4.

limitations

Chemical binding does not establish human intestinal uptake or correction of iron deficiency.

nutrient_topic

Fulvic acid collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Fulvic acid (heterogeneous humic fraction)

plain_language

The organic fraction bound ferric iron.

primary_references

EXAFS study on the reactions between iron and fulvic acid in acid aqueous solutions. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18504967/ · DOI 10.1021/es072092z

Fulvic acid: mixture identity, mineral chemistry, signaling and cross-nutrient mechanisms (2026-09-19) · lines 92–98

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cell-free EXAFS spectroscopy; acidic aqueous solutions at pH 2 and 4. · source_derived_draft · unverified_draft

## fulvic-acid-iron-complex The organic fraction bound ferric iron. The tested fulvic fraction formed iron(III) complexes within 15 minutes. Model: Cell-free EXAFS spectroscopy; acidic aqueous solutions at pH 2 and 4. Limitations: Chemical binding does not establish human intestinal uptake or correction of iron deficiency. Evidence access: Primary abstract EXAFS study on the reactions between iron and fulvic acid in acid aqueous solutions. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18504967/ · DOI 10.1021/es072092z

evidence_access

Primary abstract

experimental_model

Cell-free EXAFS study of the specified fulvic fraction.

limitations

Stomach-like acidity alone does not reproduce food, digestion, mucosal transport or human pharmacokinetics.

nutrient_topic

Fulvic acid collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Fulvic acid (heterogeneous humic fraction)

plain_language

Acidity changed the iron-redox outcome.

primary_references

EXAFS study on the reactions between iron and fulvic acid in acid aqueous solutions. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18504967/ · DOI 10.1021/es072092z

Fulvic acid: mixture identity, mineral chemistry, signaling and cross-nutrient mechanisms (2026-09-19) · lines 100–106

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cell-free EXAFS study of the specified fulvic fraction. · source_derived_draft · unverified_draft

## fulvic-acid-iron-redox Acidity changed the iron-redox outcome. Iron(III) reduction to iron(II) occurred over time at pH 2 but was not significant at pH 4. Model: Cell-free EXAFS study of the specified fulvic fraction. Limitations: Stomach-like acidity alone does not reproduce food, digestion, mucosal transport or human pharmacokinetics. Evidence access: Primary abstract EXAFS study on the reactions between iron and fulvic acid in acid aqueous solutions. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18504967/ · DOI 10.1021/es072092z

experimental_model

Purified LPO crystallography and activity assays; ammonium iodide supplied the anion, not KI.

exposure_category

Study-specific exposure, including pharmacological and in-vitro conditions; normal is the schema fallback outside the three availability categories.

limitations

Structural/biochemical model; enzyme species not assigned from abstract. Cofactor chemistry does not establish dietary iron responsiveness.

nutrient_topic

Potassium iodide research collection; shared-anion and comparator studies are not all KI interventions. · Potassium iodide

plain_language

Iron-containing heme positions peroxide in the enzyme.

primary_references

Structure of a ternary complex of lactoperoxidase with iodide and hydrogen peroxide at 1.77 Å resolution. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33882424/ · DOI 10.1016/j.jinorgbio.2021.111461

Potassium iodide: thyroid and non-thyroid mechanisms, interactions and discovery questions (2026-09-18) · lines 216–222

AI-assisted research curation; primary-study references, chemical references and label statements individually identified. Not publisher full text. · supports · Purified LPO crystallography and activity assays; ammonium iodide supplied the anion, not KI. · source_derived_draft · unverified_draft

## ki-lpo-heme Iron-containing heme positions peroxide in the enzyme. The LPO structure contains covalently attached heme; peroxide sits between its iron and distal His109. Model: Purified LPO crystallography and activity assays; ammonium iodide supplied the anion, not KI. Limitations: Structural/biochemical model; enzyme species not assigned from abstract. Cofactor chemistry does not establish dietary iron responsiveness. Evidence location: Primary abstract Structure of a ternary complex of lactoperoxidase with iodide and hydrogen peroxide at 1.77 Å resolution. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33882424/ · DOI 10.1016/j.jinorgbio.2021.111461

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Specific candidate mechanism connecting B12 function to iron utilization.

experimental_model

Before/after series of 75 patients diagnosed with cobalamin deficiency.

exposure

Blood counts and iron-status measurements before and after cobalamin therapy; regimen is not extracted from the abstract.

limitations

Proposed explanation, not a directly measured isotope flux or demonstrated cellular mediator in this study.

nutrient_topic

Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)

organism

Homo sapiens

plain_language

If red-cell production is impaired, available iron and productive iron use need not move together.

primary_references

[b12-solmaz2015] Cobalamin deficiency can mask depleted body iron reserves (2015). https://pubmed.ncbi.nlm.nih.gov/25825568/ DOI: 10.1007/s12288-014-0417-x

tissue_or_cell_type

Human blood or whole-person endpoints

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1611–1622

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Before/after series of 75 patients diagnosed with cobalamin deficiency. · source_derived_draft · unverified_draft

### b12-ineffective-erythropoiesis-iron-hypothesis The authors proposed that ineffective erythropoiesis during cobalamin deficiency reduces iron use by erythroblasts, helping explain the before/after iron results. Condition category: nutrient_deficiency nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: If red-cell production is impaired, available iron and productive iron use need not move together. organism: Homo sapiens tissue_or_cell_type: Human blood or whole-person endpoints experimental_model: Before/after series of 75 patients diagnosed with cobalamin deficiency. limitations: Proposed explanation, not a directly measured isotope flux or demonstrated cellular mediator in this study. exposure: Blood counts and iron-status measurements before and after cobalamin therapy; regimen is not extracted from the abstract. cross_nutrient: Specific candidate mechanism connecting B12 function to iron utilization. [b12-solmaz2015] Cobalamin deficiency can mask depleted body iron reserves (2015). https://pubmed.ncbi.nlm.nih.gov/25825568/ DOI: 10.1007/s12288-014-0417-x

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Retains the iron/B12 interaction without claiming either nutrient universally replaces the other.

experimental_model

Before/after series of 75 patients diagnosed with cobalamin deficiency.

exposure

Blood counts and iron-status measurements before and after cobalamin therapy; regimen is not extracted from the abstract.

limitations

A diagnostic reclassification is not proof of newly caused iron depletion.

nutrient_topic

Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)

organism

Homo sapiens

plain_language

An accompanying iron shortage could become easier to recognize during recovery.

primary_references

[b12-solmaz2015] Cobalamin deficiency can mask depleted body iron reserves (2015). https://pubmed.ncbi.nlm.nih.gov/25825568/ DOI: 10.1007/s12288-014-0417-x

tissue_or_cell_type

Human blood or whole-person endpoints

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1598–1609

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Before/after series of 75 patients diagnosed with cobalamin deficiency. · source_derived_draft · unverified_draft

### b12-repletion-iron-deficiency-detection Iron deficiency was identified in 7 of 75 patients before cobalamin therapy and 37 of 75 afterward. Condition category: nutrient_deficiency nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: An accompanying iron shortage could become easier to recognize during recovery. organism: Homo sapiens tissue_or_cell_type: Human blood or whole-person endpoints experimental_model: Before/after series of 75 patients diagnosed with cobalamin deficiency. limitations: A diagnostic reclassification is not proof of newly caused iron depletion. exposure: Blood counts and iron-status measurements before and after cobalamin therapy; regimen is not extracted from the abstract. cross_nutrient: Retains the iron/B12 interaction without claiming either nutrient universally replaces the other. [b12-solmaz2015] Cobalamin deficiency can mask depleted body iron reserves (2015). https://pubmed.ncbi.nlm.nih.gov/25825568/ DOI: 10.1007/s12288-014-0417-x

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

B12-associated ineffective blood-cell production can complicate iron-status interpretation.

experimental_model

Before/after series of 75 patients diagnosed with cobalamin deficiency.

exposure

Blood counts and iron-status measurements before and after cobalamin therapy; regimen is not extracted from the abstract.

limitations

Before/after observations cannot isolate iron utilization from all other changes.

nutrient_topic

Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)

organism

Homo sapiens

plain_language

Restoring B12 changed how the blood iron results looked.

primary_references

[b12-solmaz2015] Cobalamin deficiency can mask depleted body iron reserves (2015). https://pubmed.ncbi.nlm.nih.gov/25825568/ DOI: 10.1007/s12288-014-0417-x

tissue_or_cell_type

Human blood or whole-person endpoints

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1585–1596

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Before/after series of 75 patients diagnosed with cobalamin deficiency. · source_derived_draft · unverified_draft

### b12-repletion-iron-readouts After cobalamin therapy, mean serum iron fell from 126.4 to 59.1 micrograms/dL, ferritin from 192.5 to 44.9 ng/mL and transferrin saturation from 47.2% to 17.5%. Condition category: nutrient_deficiency nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Restoring B12 changed how the blood iron results looked. organism: Homo sapiens tissue_or_cell_type: Human blood or whole-person endpoints experimental_model: Before/after series of 75 patients diagnosed with cobalamin deficiency. limitations: Before/after observations cannot isolate iron utilization from all other changes. exposure: Blood counts and iron-status measurements before and after cobalamin therapy; regimen is not extracted from the abstract. cross_nutrient: B12-associated ineffective blood-cell production can complicate iron-status interpretation. [b12-solmaz2015] Cobalamin deficiency can mask depleted body iron reserves (2015). https://pubmed.ncbi.nlm.nih.gov/25825568/ DOI: 10.1007/s12288-014-0417-x

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Controlled sequential metabolic-unit feeding in four healthy and three chronically uremic men; histidine-deficient amino-acid diet for 35 +/- 2 days, followed by histidine-containing diet for 31 +/- 5 days.

limitations

Small historical nonrandomized sequential study; mixed renal status and artificial diet. Does not define a universal plasma cutoff, ordinary dietary prevalence or replacement dose. Changes do not identify the exact iron-handling mechanism.

nutrient_topic

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

plain_language

Red-cell production failed despite more iron in serum.

primary_references

Evidence that histidine is an essential amino acid in normal and chronically uremic man. · 1975 · https://pubmed.ncbi.nlm.nih.gov/1123426/ · DOI 10.1172/JCI108016

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

L-Histidine: supply, catabolism, histamine, receptors and cross-nutrient mechanisms (2026-09-19) · lines 42–48

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Controlled sequential metabolic-unit feeding in four healthy and three chronically uremic men; histidine-deficient amino-acid diet for 35 +/- 2 days, followed by histidine-containing diet for 31 +/- 5 days. · source_derived_draft · unverified_draft

## histidine-diet-erythropoiesis Red-cell production failed despite more iron in serum. Histidine-deficient feeding lowered hematocrit by 25 +/- 9 percent while serum iron rose; repletion produced reticulocytosis, higher hematocrit and a fall in serum iron. Model: Controlled sequential metabolic-unit feeding in four healthy and three chronically uremic men; histidine-deficient amino-acid diet for 35 +/- 2 days, followed by histidine-containing diet for 31 +/- 5 days. Limitations: Small historical nonrandomized sequential study; mixed renal status and artificial diet. Does not define a universal plasma cutoff, ordinary dietary prevalence or replacement dose. Changes do not identify the exact iron-handling mechanism. Evidence access: Primary abstract Evidence that histidine is an essential amino acid in normal and chronically uremic man. · 1975 · https://pubmed.ncbi.nlm.nih.gov/1123426/ · DOI 10.1172/JCI108016

evidence_access

Primary abstract

experimental_model

Mitochondria from mouse Cath.A-derived neuronal cells; radioactive sulfur tracing.

limitations

An isolated-organelle assembly assay is not evidence that more dietary cysteine corrects an iron–sulfur disease.

nutrient_topic

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

plain_language

Cysteine supplies the sulfur half of an iron–sulfur cofactor.

primary_references

Fe-S cluster biogenesis in isolated mammalian mitochondria: coordinated use of persulfide sulfur and iron and requirements for GTP, NADH, and ATP. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25398879/ · DOI 10.1074/jbc.M114.610402

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 268–274

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mitochondria from mouse Cath.A-derived neuronal cells; radioactive sulfur tracing. · source_derived_draft · unverified_draft

## l-cysteine-fe-s-sulfur-donor Cysteine supplies the sulfur half of an iron–sulfur cofactor. Sulfur-35 cysteine supplied sulfur for newly assembled iron–sulfur clusters incorporated into aconitase and ferredoxins in isolated mouse neuronal-cell mitochondria. Model: Mitochondria from mouse Cath.A-derived neuronal cells; radioactive sulfur tracing. Limitations: An isolated-organelle assembly assay is not evidence that more dietary cysteine corrects an iron–sulfur disease. Evidence access: Primary abstract Fe-S cluster biogenesis in isolated mammalian mitochondria: coordinated use of persulfide sulfur and iron and requirements for GTP, NADH, and ATP. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25398879/ · DOI 10.1074/jbc.M114.610402

evidence_access

Primary abstract

experimental_model

Mouse-cell isolated mitochondrial experiments.

limitations

The proposed GTPase/reductase mediators were not individually established by this study; do not assign a universal ATP requirement to each substep.

nutrient_topic

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

plain_language

The pathway has several gates, with different requirements at different steps.

primary_references

Fe-S cluster biogenesis in isolated mammalian mitochondria: coordinated use of persulfide sulfur and iron and requirements for GTP, NADH, and ATP. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25398879/ · DOI 10.1074/jbc.M114.610402

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 276–282

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

## l-cysteine-nfs1-persulfide-gate The pathway has several gates, with different requirements at different steps. Labeled NFS1-bound persulfide was an intermediate; its sulfur release required iron, GTP and NADH, whereas ATP was required for the overall assembly pathway but not this release step. Model: Mouse-cell isolated mitochondrial experiments. Limitations: The proposed GTPase/reductase mediators were not individually established by this study; do not assign a universal ATP requirement to each substep. Evidence access: Primary abstract Fe-S cluster biogenesis in isolated mammalian mitochondria: coordinated use of persulfide sulfur and iron and requirements for GTP, NADH, and ATP. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25398879/ · DOI 10.1074/jbc.M114.610402

cross_nutrient

true

evidence_span

{"source_cache": "artifacts/iodine-synthesis-sources/9492031.json", "json_field": "abstractText", "text_sha256": "4a73f43b4e982a85a7e632cc57a8db51a590eb23fa1d578a448cab52b2d8405f", "text_characters": 2006, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."}

experimental_model

Recombinant human TPO ectodomain residues 1–848 expressed in Chinese hamster ovary cells

exposure

1 mg/L hemin, hematin or protoporphyrin IX in expression cultures; human ectodomain 1–848.

limitations

Guaiacol assay and recombinant construct; not a human dietary iron-repletion experiment.

nutrient_topic

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

organism

Homo sapiens protein; Cricetulus griseus host cells

plain_language

Iron-containing heme helps TPO become an active enzyme.

primary_references

[iodine-syn-tpo1998] The greater glycan content of recombinant human thyroid peroxidase of mammalian than of insect cell origin facilitates purification to homogeneity of enzymatically protein remaining soluble at high concentration. (1998). https://pubmed.ncbi.nlm.nih.gov/9492031/ DOI: 10.1210/endo.139.3.5782

tissue_or_cell_type

CHO expression system; purified protein

Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 562–574

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human TPO ectodomain residues 1–848 expressed in Chinese hamster ovary cells · source_derived_draft · unverified_draft

### iodine-syn-heme-activity Adding hemin or hematin to CHO expression cultures increased heme incorporation and guaiacol activity of purified human TPO ectodomain relative to the iron-free porphyrin comparison. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Iron-containing heme helps TPO become an active enzyme. organism: Homo sapiens protein; Cricetulus griseus host cells tissue_or_cell_type: CHO expression system; purified protein experimental_model: Recombinant human TPO ectodomain residues 1–848 expressed in Chinese hamster ovary cells limitations: Guaiacol assay and recombinant construct; not a human dietary iron-repletion experiment. exposure: 1 mg/L hemin, hematin or protoporphyrin IX in expression cultures; human ectodomain 1–848. cross_nutrient: true evidence_span: {"source_cache": "artifacts/iodine-synthesis-sources/9492031.json", "json_field": "abstractText", "text_sha256": "4a73f43b4e982a85a7e632cc57a8db51a590eb23fa1d578a448cab52b2d8405f", "text_characters": 2006, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."} [iodine-syn-tpo1998] The greater glycan content of recombinant human thyroid peroxidase of mammalian than of insect cell origin facilitates purification to homogeneity of enzymatically protein remaining soluble at high concentration. (1998). https://pubmed.ncbi.nlm.nih.gov/9492031/ DOI: 10.1210/endo.139.3.5782

cross_nutrient

true

evidence_span

{"source_cache": "artifacts/iodine-synthesis-sources/10187846.json", "json_field": "abstractText", "text_sha256": "97f8a86c7effd5754e2b61c65d769de9e86678a7398c5eb20a0e88ac49a8fdbb", "text_characters": 1855, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."}

experimental_model

CHO cells expressing human TPO; additional primary thyroid cultures

exposure

Succinylacetone; concentration not stated in abstract.

limitations

Pharmacological heme synthesis perturbation; not evidence of a dietary iron threshold.

nutrient_topic

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

organism

Homo sapiens protein; Cricetulus griseus host cells

plain_language

Blocking heme production kept much of TPO from reaching the surface.

primary_references

[iodine-syn-tpo1999] Role of heme in intracellular trafficking of thyroperoxidase and involvement of H2O2 generated at the apical surface of thyroid cells in autocatalytic covalent heme binding. (1999). https://pubmed.ncbi.nlm.nih.gov/10187846/ DOI: 10.1074/jbc.274.15.10533

tissue_or_cell_type

CHO endoplasmic reticulum and cell surface

Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 576–588

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · CHO cells expressing human TPO; additional primary thyroid cultures · source_derived_draft · unverified_draft

### iodine-syn-heme-trafficking In CHO cells expressing human TPO, inhibition of heme biosynthesis by succinylacetone decreased surface TPO expression by approximately 80%. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Blocking heme production kept much of TPO from reaching the surface. organism: Homo sapiens protein; Cricetulus griseus host cells tissue_or_cell_type: CHO endoplasmic reticulum and cell surface experimental_model: CHO cells expressing human TPO; additional primary thyroid cultures limitations: Pharmacological heme synthesis perturbation; not evidence of a dietary iron threshold. exposure: Succinylacetone; concentration not stated in abstract. cross_nutrient: true evidence_span: {"source_cache": "artifacts/iodine-synthesis-sources/10187846.json", "json_field": "abstractText", "text_sha256": "97f8a86c7effd5754e2b61c65d769de9e86678a7398c5eb20a0e88ac49a8fdbb", "text_characters": 1855, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."} [iodine-syn-tpo1999] Role of heme in intracellular trafficking of thyroperoxidase and involvement of H2O2 generated at the apical surface of thyroid cells in autocatalytic covalent heme binding. (1999). https://pubmed.ncbi.nlm.nih.gov/10187846/ DOI: 10.1074/jbc.274.15.10533

cross_nutrient

true

evidence_span

{"source_cache": "artifacts/iodine-synthesis-sources/10187846.json", "json_field": "abstractText", "text_sha256": "97f8a86c7effd5754e2b61c65d769de9e86678a7398c5eb20a0e88ac49a8fdbb", "text_characters": 1855, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."}

experimental_model

CHO cells expressing human TPO; additional primary thyroid cultures

exposure

10 micromolar H2O2, 10 minutes.

limitations

Authors interpret activation through covalent heme attachment; no direct nutrient-intake intervention.

nutrient_topic

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

organism

Homo sapiens protein; Cricetulus griseus host cells

plain_language

Peroxide exposure helped activate surface TPO in this cell model.

primary_references

[iodine-syn-tpo1999] Role of heme in intracellular trafficking of thyroperoxidase and involvement of H2O2 generated at the apical surface of thyroid cells in autocatalytic covalent heme binding. (1999). https://pubmed.ncbi.nlm.nih.gov/10187846/ DOI: 10.1074/jbc.274.15.10533

tissue_or_cell_type

CHO cell surface

Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 590–602

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · CHO cells expressing human TPO; additional primary thyroid cultures · source_derived_draft · unverified_draft

### iodine-syn-peroxide-tpo-activation Exposing human TPO-expressing CHO cells to 10 micromolar H2O2 for 10 minutes increased cell-surface peroxidase activity by 65%. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Peroxide exposure helped activate surface TPO in this cell model. organism: Homo sapiens protein; Cricetulus griseus host cells tissue_or_cell_type: CHO cell surface experimental_model: CHO cells expressing human TPO; additional primary thyroid cultures limitations: Authors interpret activation through covalent heme attachment; no direct nutrient-intake intervention. exposure: 10 micromolar H2O2, 10 minutes. cross_nutrient: true evidence_span: {"source_cache": "artifacts/iodine-synthesis-sources/10187846.json", "json_field": "abstractText", "text_sha256": "97f8a86c7effd5754e2b61c65d769de9e86678a7398c5eb20a0e88ac49a8fdbb", "text_characters": 1855, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."} [iodine-syn-tpo1999] Role of heme in intracellular trafficking of thyroperoxidase and involvement of H2O2 generated at the apical surface of thyroid cells in autocatalytic covalent heme binding. (1999). https://pubmed.ncbi.nlm.nih.gov/10187846/ DOI: 10.1074/jbc.274.15.10533

cross_nutrient

true

evidence_span

{"source_cache": "artifacts/iodine-synthesis-sources/36537574.txt", "start_char": 17835, "end_char": 18855, "text_sha256": "6771d21482631bf712dfa882f1d08e4f40e02507211c65a60c7ef47f0d02e5d4", "text_characters": 1020, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."}

experimental_model

Cryo-EM of recombinant human TPO extracellular domain with antibody fragments

exposure

Human TPO residues 1–839 expressed in High Five insect cells and bound to 2G4 or 4F5 antibody fragments.

limitations

A structural observation; no selenium catalytic requirement or dietary iron dose is demonstrated.

nutrient_topic

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

organism

Homo sapiens protein; Trichoplusia ni expression cells

plain_language

TPO contains an iron-bearing heme group at its catalytic center.

primary_references

[iodine-syn-tpo2023] Cryo-electron microscopy structures of human thyroid peroxidase (TPO) in complex with TPO antibodies. (2023). https://pubmed.ncbi.nlm.nih.gov/36537574/ DOI: 10.1530/jme-22-0149

tissue_or_cell_type

Purified extracellular-domain antibody complexes

Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 604–616

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cryo-EM of recombinant human TPO extracellular domain with antibody fragments · source_derived_draft · unverified_draft

### iodine-syn-tpo-heme-structure Cryo-EM structures of the human TPO extracellular domain resolve heme at the peroxidase active site. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: TPO contains an iron-bearing heme group at its catalytic center. organism: Homo sapiens protein; Trichoplusia ni expression cells tissue_or_cell_type: Purified extracellular-domain antibody complexes experimental_model: Cryo-EM of recombinant human TPO extracellular domain with antibody fragments limitations: A structural observation; no selenium catalytic requirement or dietary iron dose is demonstrated. exposure: Human TPO residues 1–839 expressed in High Five insect cells and bound to 2G4 or 4F5 antibody fragments. cross_nutrient: true evidence_span: {"source_cache": "artifacts/iodine-synthesis-sources/36537574.txt", "start_char": 17835, "end_char": 18855, "text_sha256": "6771d21482631bf712dfa882f1d08e4f40e02507211c65a60c7ef47f0d02e5d4", "text_characters": 1020, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."} [iodine-syn-tpo2023] Cryo-electron microscopy structures of human thyroid peroxidase (TPO) in complex with TPO antibodies. (2023). https://pubmed.ncbi.nlm.nih.gov/36537574/ DOI: 10.1530/jme-22-0149

evidence_span

{"source_cache": "artifacts/cold-research/9753429.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3c76ec6d5dadb463c0a044175d5a78fbd02df4da7c339029c8c232e8878175b9", "start_char": 0, "end_char": 1695, "text_sha256": "3c76ec6d5dadb463c0a044175d5a78fbd02df4da7c339029c8c232e8878175b9"}

experimental_model

Crystal structure of rat tyrosine hydroxylase with a cofactor analogue and iron at 2.3 angstrom

exposure

Bound 7,8-dihydrobiopterin and iron

limitations

Structural chemistry of the rate-limiting step. It is a rat enzyme structure with a cofactor analogue, not a measurement of iron status in an animal.

nutrient_topic

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

organism

Rat enzyme

plain_language

The oxygen molecule slots into the gap between the cofactor and the iron.

primary_references

[cold-p9753429] Crystal structure of tyrosine hydroxylase with bound cofactor analogue and iron at 2.3 A resolution: self-hydroxylation of Phe300 and the pterin-binding site. (1998). https://pubmed.ncbi.nlm.nih.gov/9753429/ DOI: 10.1021/bi981462g

tissue_or_cell_type

Purified catalytic and tetramerization domains

Cold water immersion: cold sensing, heat production, the catecholamine axis and what repeated exposure changes (2026-09-19) · lines 546–557

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Crystal structure of rat tyrosine hydroxylase with a cofactor analogue and iron at 2.3 angstrom · source_derived_draft · unverified_draft

### cold-th-pterin-geometry The pterin binds in the active-site cleft forming an aromatic stacking interaction with Phe300, which is itself hydroxylated in the meta position by an autocatalytic process and anchored by a hydrogen bond to the carbonyl of Gln310; the iron sits 5.6 angstrom from the pterin 4a carbon, and molecular oxygen could bind in a bridging position between the pterin and the iron before substrate hydroxylation. Condition category: normal nutrient_topic: Cold water immersion research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: The oxygen molecule slots into the gap between the cofactor and the iron. organism: Rat enzyme tissue_or_cell_type: Purified catalytic and tetramerization domains experimental_model: Crystal structure of rat tyrosine hydroxylase with a cofactor analogue and iron at 2.3 angstrom limitations: Structural chemistry of the rate-limiting step. It is a rat enzyme structure with a cofactor analogue, not a measurement of iron status in an animal. exposure: Bound 7,8-dihydrobiopterin and iron evidence_span: {"source_cache": "artifacts/cold-research/9753429.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3c76ec6d5dadb463c0a044175d5a78fbd02df4da7c339029c8c232e8878175b9", "start_char": 0, "end_char": 1695, "text_sha256": "3c76ec6d5dadb463c0a044175d5a78fbd02df4da7c339029c8c232e8878175b9"} [cold-p9753429] Crystal structure of tyrosine hydroxylase with bound cofactor analogue and iron at 2.3 A resolution: self-hydroxylation of Phe300 and the pterin-binding site. (1998). https://pubmed.ncbi.nlm.nih.gov/9753429/ DOI: 10.1021/bi981462g

evidence_span

{"source_cache": "artifacts/cold-research/10396606.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "fdd2deec82fad8f9e148848c443d5b173ec42c0e07d9045c59773f7109883a7b", "start_char": 0, "end_char": 1139, "text_sha256": "fdd2deec82fad8f9e148848c443d5b173ec42c0e07d9045c59773f7109883a7b"}

experimental_model

Winter swimmers compared with people who had never taken part, sampled for erythrocyte and plasma antioxidants

exposure

Habitual ice bathing

limitations

A cross-sectional comparison, so self-selection cannot be excluded. The authors frame it as adaptation to repeated oxidative stress.

nutrient_topic

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

organism

Human

plain_language

People who swim in ice water carry more antioxidant defence at rest.

primary_references

[cold-p10396606] Improved antioxidative protection in winter swimmers. (1999). https://pubmed.ncbi.nlm.nih.gov/10396606/ DOI: 10.1093/qjmed/92.4.193

tissue_or_cell_type

Erythrocytes and plasma

Cold water immersion: cold sensing, heat production, the catecholamine axis and what repeated exposure changes (2026-09-19) · lines 689–700

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Winter swimmers compared with people who had never taken part, sampled for erythrocyte and plasma antioxidants · source_derived_draft · unverified_draft

### cold-winter-swimmer-antioxidants Baseline reduced glutathione concentration and erythrocyte superoxide dismutase and catalase activities were higher in winter swimmers than in controls, which the authors interpret as an adaptive response to repeated oxidative stress and postulate as a mechanism of increased tolerance to environmental stress. Condition category: normal nutrient_topic: Cold water immersion research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: People who swim in ice water carry more antioxidant defence at rest. organism: Human tissue_or_cell_type: Erythrocytes and plasma experimental_model: Winter swimmers compared with people who had never taken part, sampled for erythrocyte and plasma antioxidants limitations: A cross-sectional comparison, so self-selection cannot be excluded. The authors frame it as adaptation to repeated oxidative stress. exposure: Habitual ice bathing evidence_span: {"source_cache": "artifacts/cold-research/10396606.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "fdd2deec82fad8f9e148848c443d5b173ec42c0e07d9045c59773f7109883a7b", "start_char": 0, "end_char": 1139, "text_sha256": "fdd2deec82fad8f9e148848c443d5b173ec42c0e07d9045c59773f7109883a7b"} [cold-p10396606] Improved antioxidative protection in winter swimmers. (1999). https://pubmed.ncbi.nlm.nih.gov/10396606/ DOI: 10.1093/qjmed/92.4.193

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

Ferrous fumarate (added_treatment); Calcium disodium edetate (concurrent_treatment); Iron (interacting_nutrient); Manganese (affected_nutrient)

evidence_span

{"source_cache": "artifacts/manganese-clinical-sources/stamelou2012.txt", "locator": "Clinical description; age 15–16 treatment changes", "file_sha256": "5d86a26fe564508fb382d1c8df61f531bfbaf06b69e2078b0999e3a3129555f6", "start_char": 9842, "end_char": 10521, "text_sha256": "2da91cbaa297984ac1c90caf8701ce0a3f9a633b806ef4fff178b6ecc46c8aa1", "text_characters": 679}

experimental_model

Ten-year longitudinal report of one SLC30A10 patient

exposure

Calcium disodium edetate chelation; subsequent increase in chelation frequency and addition of oral ferrous fumarate.

limitations

Repeated observations in one previously described patient. Combined treatment changes prevent attribution of later benefit to iron alone; disease-specific treatment is not routine nutrient replacement.

nutrient_topic

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

organism

Homo sapiens

plain_language

The combined regimen affected both manganese removal and iron status.

primary_references

[mn-clin-stamelou2012] Dystonia with brain manganese accumulation resulting from SLC30A10 mutations: a new treatable disorder. (2012). https://pubmed.ncbi.nlm.nih.gov/22926781/ DOI: 10.1002/mds.25138

tissue_or_cell_type

Urine, blood, brain MRI and motor function

trigger_kind

machinery_impairment Imported condition classification; unverified.

Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 1314–1326

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ten-year longitudinal report of one SLC30A10 patient · source_derived_draft · unverified_draft

### mn-clin-iron-chelation-combination After more frequent chelation and added ferrous fumarate, blood manganese, MRI and liver findings improved; later iron dosing was reduced after serum iron rose excessively. Condition category: machinery_impairment nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: The combined regimen affected both manganese removal and iron status. organism: Homo sapiens tissue_or_cell_type: Urine, blood, brain MRI and motor function experimental_model: Ten-year longitudinal report of one SLC30A10 patient limitations: Repeated observations in one previously described patient. Combined treatment changes prevent attribution of later benefit to iron alone; disease-specific treatment is not routine nutrient replacement. exposure: Calcium disodium edetate chelation; subsequent increase in chelation frequency and addition of oral ferrous fumarate. cross_nutrient: Ferrous fumarate (added_treatment); Calcium disodium edetate (concurrent_treatment); Iron (interacting_nutrient); Manganese (affected_nutrient) evidence_span: {"source_cache": "artifacts/manganese-clinical-sources/stamelou2012.txt", "locator": "Clinical description; age 15–16 treatment changes", "file_sha256": "5d86a26fe564508fb382d1c8df61f531bfbaf06b69e2078b0999e3a3129555f6", "start_char": 9842, "end_char": 10521, "text_sha256": "2da91cbaa297984ac1c90caf8701ce0a3f9a633b806ef4fff178b6ecc46c8aa1", "text_characters": 679} [mn-clin-stamelou2012] Dystonia with brain manganese accumulation resulting from SLC30A10 mutations: a new treatable disorder. (2012). https://pubmed.ncbi.nlm.nih.gov/22926781/ DOI: 10.1002/mds.25138

availability_state

biomarker_context Imported condition classification; unverified.

cross_nutrient

Iron (interacting_nutrient); Manganese (absorbed_nutrient)

evidence_span

{"source_cache": "artifacts/manganese-clinical-sources/finley1999.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "3ec791f205459093fec1dfac522bbb6241aa1199894886be9c64d4c2eb2b97d7", "start_char": 0, "end_char": 1731, "text_sha256": "3ec791f205459093fec1dfac522bbb6241aa1199894886be9c64d4c2eb2b97d7", "text_characters": 1731}

experimental_model

Crossover isotope study in 26 healthy young women

exposure

Eleven women with serum ferritin >50 micrograms/L and 15 with <15 micrograms/L; diets at 0.7 or 9.5 mg Mn/day for 60 days each.

limitations

Ferritin defines the comparison groups, not cellular manganese deficiency. Retention and absorption are separate measurements; the study does not identify a specific transporter as their cause.

nutrient_topic

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

organism

Homo sapiens

plain_language

The amount of manganese absorbed depended partly on iron stores.

primary_references

[mn-clin-finley1999] Manganese absorption and retention by young women is associated with serum ferritin concentration. (1999). https://pubmed.ncbi.nlm.nih.gov/10393136/ DOI: 10.1093/ajcn/70.1.37

tissue_or_cell_type

Gut, whole-body tracer retention and blood

trigger_kind

biomarker_context Imported condition classification; unverified.

Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 978–990

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Crossover isotope study in 26 healthy young women · source_derived_draft · unverified_draft

### mn-clin-iron-stores-absorption Manganese absorption was greatest in the low-ferritin group on the low-manganese diet and lowest in the high-ferritin group. Condition category: biomarker_context nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: The amount of manganese absorbed depended partly on iron stores. organism: Homo sapiens tissue_or_cell_type: Gut, whole-body tracer retention and blood experimental_model: Crossover isotope study in 26 healthy young women limitations: Ferritin defines the comparison groups, not cellular manganese deficiency. Retention and absorption are separate measurements; the study does not identify a specific transporter as their cause. exposure: Eleven women with serum ferritin >50 micrograms/L and 15 with <15 micrograms/L; diets at 0.7 or 9.5 mg Mn/day for 60 days each. cross_nutrient: Iron (interacting_nutrient); Manganese (absorbed_nutrient) evidence_span: {"source_cache": "artifacts/manganese-clinical-sources/finley1999.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "3ec791f205459093fec1dfac522bbb6241aa1199894886be9c64d4c2eb2b97d7", "start_char": 0, "end_char": 1731, "text_sha256": "3ec791f205459093fec1dfac522bbb6241aa1199894886be9c64d4c2eb2b97d7", "text_characters": 1731} [mn-clin-finley1999] Manganese absorption and retention by young women is associated with serum ferritin concentration. (1999). https://pubmed.ncbi.nlm.nih.gov/10393136/ DOI: 10.1093/ajcn/70.1.37

availability_state

biomarker_context Imported condition classification; unverified.

cross_nutrient

Iron (associated_nutrient)

evidence_span

{"source_cache": "artifacts/manganese-clinical-sources/finley1999.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "3ec791f205459093fec1dfac522bbb6241aa1199894886be9c64d4c2eb2b97d7", "start_char": 0, "end_char": 1731, "text_sha256": "3ec791f205459093fec1dfac522bbb6241aa1199894886be9c64d4c2eb2b97d7", "text_characters": 1731}

experimental_model

Crossover isotope study in 26 healthy young women

exposure

Eleven women with serum ferritin >50 micrograms/L and 15 with <15 micrograms/L; diets at 0.7 or 9.5 mg Mn/day for 60 days each.

limitations

Ferritin defines the comparison groups, not cellular manganese deficiency. Retention and absorption are separate measurements; the study does not identify a specific transporter as their cause.

nutrient_topic

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

organism

Homo sapiens

plain_language

An enzyme readout also varied with iron stores.

primary_references

[mn-clin-finley1999] Manganese absorption and retention by young women is associated with serum ferritin concentration. (1999). https://pubmed.ncbi.nlm.nih.gov/10393136/ DOI: 10.1093/ajcn/70.1.37

tissue_or_cell_type

Gut, whole-body tracer retention and blood

trigger_kind

biomarker_context Imported condition classification; unverified.

Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 1006–1018

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Crossover isotope study in 26 healthy young women · source_derived_draft · unverified_draft

### mn-clin-iron-stores-arginase The high-ferritin group had lower measured arginase activity in the controlled dietary comparison. Condition category: biomarker_context nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: An enzyme readout also varied with iron stores. organism: Homo sapiens tissue_or_cell_type: Gut, whole-body tracer retention and blood experimental_model: Crossover isotope study in 26 healthy young women limitations: Ferritin defines the comparison groups, not cellular manganese deficiency. Retention and absorption are separate measurements; the study does not identify a specific transporter as their cause. exposure: Eleven women with serum ferritin >50 micrograms/L and 15 with <15 micrograms/L; diets at 0.7 or 9.5 mg Mn/day for 60 days each. cross_nutrient: Iron (associated_nutrient) evidence_span: {"source_cache": "artifacts/manganese-clinical-sources/finley1999.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "3ec791f205459093fec1dfac522bbb6241aa1199894886be9c64d4c2eb2b97d7", "start_char": 0, "end_char": 1731, "text_sha256": "3ec791f205459093fec1dfac522bbb6241aa1199894886be9c64d4c2eb2b97d7", "text_characters": 1731} [mn-clin-finley1999] Manganese absorption and retention by young women is associated with serum ferritin concentration. (1999). https://pubmed.ncbi.nlm.nih.gov/10393136/ DOI: 10.1093/ajcn/70.1.37

availability_state

biomarker_context Imported condition classification; unverified.

cross_nutrient

Iron (interacting_nutrient); Manganese (retained_nutrient)

evidence_span

{"source_cache": "artifacts/manganese-clinical-sources/finley1999.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "3ec791f205459093fec1dfac522bbb6241aa1199894886be9c64d4c2eb2b97d7", "start_char": 0, "end_char": 1731, "text_sha256": "3ec791f205459093fec1dfac522bbb6241aa1199894886be9c64d4c2eb2b97d7", "text_characters": 1731}

experimental_model

Crossover isotope study in 26 healthy young women

exposure

Eleven women with serum ferritin >50 micrograms/L and 15 with <15 micrograms/L; diets at 0.7 or 9.5 mg Mn/day for 60 days each.

limitations

Ferritin defines the comparison groups, not cellular manganese deficiency. Retention and absorption are separate measurements; the study does not identify a specific transporter as their cause.

nutrient_topic

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

organism

Homo sapiens

plain_language

Absorbing manganese and keeping it are separately regulated.

primary_references

[mn-clin-finley1999] Manganese absorption and retention by young women is associated with serum ferritin concentration. (1999). https://pubmed.ncbi.nlm.nih.gov/10393136/ DOI: 10.1093/ajcn/70.1.37

tissue_or_cell_type

Gut, whole-body tracer retention and blood

trigger_kind

biomarker_context Imported condition classification; unverified.

Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 992–1004

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Crossover isotope study in 26 healthy young women · source_derived_draft · unverified_draft

### mn-clin-iron-stores-retention Tracer half-life was longest with high ferritin and low manganese intake, and shortest during the high-manganese diets. Condition category: biomarker_context nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Absorbing manganese and keeping it are separately regulated. organism: Homo sapiens tissue_or_cell_type: Gut, whole-body tracer retention and blood experimental_model: Crossover isotope study in 26 healthy young women limitations: Ferritin defines the comparison groups, not cellular manganese deficiency. Retention and absorption are separate measurements; the study does not identify a specific transporter as their cause. exposure: Eleven women with serum ferritin >50 micrograms/L and 15 with <15 micrograms/L; diets at 0.7 or 9.5 mg Mn/day for 60 days each. cross_nutrient: Iron (interacting_nutrient); Manganese (retained_nutrient) evidence_span: {"source_cache": "artifacts/manganese-clinical-sources/finley1999.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "3ec791f205459093fec1dfac522bbb6241aa1199894886be9c64d4c2eb2b97d7", "start_char": 0, "end_char": 1731, "text_sha256": "3ec791f205459093fec1dfac522bbb6241aa1199894886be9c64d4c2eb2b97d7", "text_characters": 1731} [mn-clin-finley1999] Manganese absorption and retention by young women is associated with serum ferritin concentration. (1999). https://pubmed.ncbi.nlm.nih.gov/10393136/ DOI: 10.1093/ajcn/70.1.37

cross_nutrient

Heme iron (comparison_form); Serum manganese concentration (associated_endpoint); Urinary manganese excretion (associated_endpoint); Manganese (affected_nutrient); Iron (associated_nutrient)

evidence_span

{"source_cache": "artifacts/manganese-clinical-sources/davis1992b.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "8542f3e0bd8f5903e6ce9e30fba2a6d7797a822ab1aeeab992659ba482533102", "start_char": 0, "end_char": 1172, "text_sha256": "8542f3e0bd8f5903e6ce9e30fba2a6d7797a822ab1aeeab992659ba482533102", "text_characters": 1172}

experimental_model

Dietary association analysis in 47 women consuming usual diets

exposure

Comparisons of manganese, heme-iron and nonheme-iron intake.

limitations

Observational food-pattern associations cannot isolate a transporter or iron itself from correlated dietary factors. This may analyze participants related to the companion supplementation report; papers are not independent trials.

nutrient_topic

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

organism

Homo sapiens

plain_language

Food form and the rest of the diet changed the observed iron–manganese relationship.

primary_references

[mn-clin-davis1992b] Interactions among dietary manganese, heme iron, and nonheme iron in women. (1992). https://pubmed.ncbi.nlm.nih.gov/1415012/ DOI: 10.1093/ajcn/56.5.926

tissue_or_cell_type

Serum, urine and lymphocyte enzymes

Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 1160–1172

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dietary association analysis in 47 women consuming usual diets · source_derived_draft · unverified_draft

### mn-clin-nonheme-association Higher nonheme-iron intake was associated with lower serum and urinary manganese and lymphocyte MnSOD activity; heme-iron intake showed no consistent manganese pattern. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Food form and the rest of the diet changed the observed iron–manganese relationship. organism: Homo sapiens tissue_or_cell_type: Serum, urine and lymphocyte enzymes experimental_model: Dietary association analysis in 47 women consuming usual diets limitations: Observational food-pattern associations cannot isolate a transporter or iron itself from correlated dietary factors. This may analyze participants related to the companion supplementation report; papers are not independent trials. exposure: Comparisons of manganese, heme-iron and nonheme-iron intake. cross_nutrient: Heme iron (comparison_form); Serum manganese concentration (associated_endpoint); Urinary manganese excretion (associated_endpoint); Manganese (affected_nutrient); Iron (associated_nutrient) evidence_span: {"source_cache": "artifacts/manganese-clinical-sources/davis1992b.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "8542f3e0bd8f5903e6ce9e30fba2a6d7797a822ab1aeeab992659ba482533102", "start_char": 0, "end_char": 1172, "text_sha256": "8542f3e0bd8f5903e6ce9e30fba2a6d7797a822ab1aeeab992659ba482533102", "text_characters": 1172} [mn-clin-davis1992b] Interactions among dietary manganese, heme iron, and nonheme iron in women. (1992). https://pubmed.ncbi.nlm.nih.gov/1415012/ DOI: 10.1093/ajcn/56.5.926

cross_nutrient

Plasma ferritin concentration (associated_biomarker); Iron (possible_context)

evidence_span

{"source_cache": "artifacts/manganese-clinical-sources/finley1994.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "f24059b0e56ddb384da59918af300da971697d38bdac6be5775a39d65f5209a0", "start_char": 0, "end_char": 1009, "text_sha256": "f24059b0e56ddb384da59918af300da971697d38bdac6be5775a39d65f5209a0", "text_characters": 1009}

experimental_model

Whole-body manganese tracer study in 20 men and 20 women

exposure

Adequate-manganese diet and oral tracer meal; counting continued for 70 days.

limitations

Sex-associated findings may reflect iron status and other differences. Reported tracer-activity units in the abstract were not independently verified and are not used here.

nutrient_topic

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

organism

Homo sapiens

plain_language

Lower absorption did not mean faster loss afterward.

primary_references

[mn-clin-finley1994] Sex affects manganese absorption and retention by humans from a diet adequate in manganese. (1994). https://pubmed.ncbi.nlm.nih.gov/7985639/ DOI: 10.1093/ajcn/60.6.949

tissue_or_cell_type

Intestinal absorption and whole-body retention

Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 1076–1088

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Whole-body manganese tracer study in 20 men and 20 women · source_derived_draft · unverified_draft

### mn-clin-sex-absorption-retention Men absorbed less manganese tracer than women but retained the absorbed tracer for longer. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Lower absorption did not mean faster loss afterward. organism: Homo sapiens tissue_or_cell_type: Intestinal absorption and whole-body retention experimental_model: Whole-body manganese tracer study in 20 men and 20 women limitations: Sex-associated findings may reflect iron status and other differences. Reported tracer-activity units in the abstract were not independently verified and are not used here. exposure: Adequate-manganese diet and oral tracer meal; counting continued for 70 days. cross_nutrient: Plasma ferritin concentration (associated_biomarker); Iron (possible_context) evidence_span: {"source_cache": "artifacts/manganese-clinical-sources/finley1994.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "f24059b0e56ddb384da59918af300da971697d38bdac6be5775a39d65f5209a0", "start_char": 0, "end_char": 1009, "text_sha256": "f24059b0e56ddb384da59918af300da971697d38bdac6be5775a39d65f5209a0", "text_characters": 1009} [mn-clin-finley1994] Sex affects manganese absorption and retention by humans from a diet adequate in manganese. (1994). https://pubmed.ncbi.nlm.nih.gov/7985639/ DOI: 10.1093/ajcn/60.6.949

cross_nutrient

Iron (measured_nutrient)

evidence_span

{"source_cache": "artifacts/manganese-clinical-sources/davis1992a.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "2fbf15cf32ba80f68c4f4efaa7fa50de76b90094438325cc6632b7d447e22227", "start_char": 0, "end_char": 956, "text_sha256": "2fbf15cf32ba80f68c4f4efaa7fa50de76b90094438325cc6632b7d447e22227", "text_characters": 956}

experimental_model

124-day supplementation study in 47 women

exposure

Placebo, 60 mg iron/day, 15 mg manganese/day or both.

limitations

Historical experimental doses, not intake advice. Abstract reports manganese changes from baseline; biomarkers do not demonstrate improved health or establish a deficiency threshold.

nutrient_topic

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

organism

Homo sapiens

plain_language

An interaction need not produce a detectable change in both minerals.

primary_references

[mn-clin-davis1992a] Longitudinal changes of manganese-dependent superoxide dismutase and other indexes of manganese and iron status in women. (1992). https://pubmed.ncbi.nlm.nih.gov/1550052/ DOI: 10.1093/ajcn/55.3.747

tissue_or_cell_type

Lymphocytes, serum and urine

Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 1146–1158

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 124-day supplementation study in 47 women · source_derived_draft · unverified_draft

### mn-clin-supplement-iron-null Manganese supplementation did not change any measured indices of iron status. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: An interaction need not produce a detectable change in both minerals. organism: Homo sapiens tissue_or_cell_type: Lymphocytes, serum and urine experimental_model: 124-day supplementation study in 47 women limitations: Historical experimental doses, not intake advice. Abstract reports manganese changes from baseline; biomarkers do not demonstrate improved health or establish a deficiency threshold. exposure: Placebo, 60 mg iron/day, 15 mg manganese/day or both. cross_nutrient: Iron (measured_nutrient) evidence_span: {"source_cache": "artifacts/manganese-clinical-sources/davis1992a.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "2fbf15cf32ba80f68c4f4efaa7fa50de76b90094438325cc6632b7d447e22227", "start_char": 0, "end_char": 956, "text_sha256": "2fbf15cf32ba80f68c4f4efaa7fa50de76b90094438325cc6632b7d447e22227", "text_characters": 956} [mn-clin-davis1992a] Longitudinal changes of manganese-dependent superoxide dismutase and other indexes of manganese and iron status in women. (1992). https://pubmed.ncbi.nlm.nih.gov/1550052/ DOI: 10.1093/ajcn/55.3.747

cross_nutrient

Mitochondrial superoxide dismutase / SOD2 (measured_enzyme); Iron (factorial_comparator)

evidence_span

{"source_cache": "artifacts/manganese-clinical-sources/davis1992a.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "2fbf15cf32ba80f68c4f4efaa7fa50de76b90094438325cc6632b7d447e22227", "start_char": 0, "end_char": 956, "text_sha256": "2fbf15cf32ba80f68c4f4efaa7fa50de76b90094438325cc6632b7d447e22227", "text_characters": 956}

experimental_model

124-day supplementation study in 47 women

exposure

Placebo, 60 mg iron/day, 15 mg manganese/day or both.

limitations

Historical experimental doses, not intake advice. Abstract reports manganese changes from baseline; biomarkers do not demonstrate improved health or establish a deficiency threshold.

nutrient_topic

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

organism

Homo sapiens

plain_language

The manganese enzyme responded in the sampled immune cells.

primary_references

[mn-clin-davis1992a] Longitudinal changes of manganese-dependent superoxide dismutase and other indexes of manganese and iron status in women. (1992). https://pubmed.ncbi.nlm.nih.gov/1550052/ DOI: 10.1093/ajcn/55.3.747

tissue_or_cell_type

Lymphocytes, serum and urine

Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 1104–1116

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 124-day supplementation study in 47 women · source_derived_draft · unverified_draft

### mn-clin-supplement-lymphocyte-sod Manganese supplementation increased lymphocyte MnSOD activity from baseline. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: The manganese enzyme responded in the sampled immune cells. organism: Homo sapiens tissue_or_cell_type: Lymphocytes, serum and urine experimental_model: 124-day supplementation study in 47 women limitations: Historical experimental doses, not intake advice. Abstract reports manganese changes from baseline; biomarkers do not demonstrate improved health or establish a deficiency threshold. exposure: Placebo, 60 mg iron/day, 15 mg manganese/day or both. cross_nutrient: Mitochondrial superoxide dismutase / SOD2 (measured_enzyme); Iron (factorial_comparator) evidence_span: {"source_cache": "artifacts/manganese-clinical-sources/davis1992a.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "2fbf15cf32ba80f68c4f4efaa7fa50de76b90094438325cc6632b7d447e22227", "start_char": 0, "end_char": 956, "text_sha256": "2fbf15cf32ba80f68c4f4efaa7fa50de76b90094438325cc6632b7d447e22227", "text_characters": 956} [mn-clin-davis1992a] Longitudinal changes of manganese-dependent superoxide dismutase and other indexes of manganese and iron status in women. (1992). https://pubmed.ncbi.nlm.nih.gov/1550052/ DOI: 10.1093/ajcn/55.3.747

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Dietary Mn:Fe balance affected mouse Sod2 metal occupancy.

experimental_model

Purified SOD2, SOD2-overexpressing human cells, and dietary C57BL/6J mouse experiments

exposure

Four weeks of 40 ppm Mn/275 ppm Fe versus 150 ppm Mn/275 ppm Fe control.

limitations

Primary experimental scope only; no human dietary threshold, clinical treatment rule, or universal metal substitution is established.

nutrient_topic

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

organism

Mus musculus

plain_language

Lower dietary manganese relative to iron changed liver Sod2 metal loading in mice.

primary_references

[mn-enz-29398562] Switch of Mitochondrial Superoxide Dismutase into a Prooxidant Peroxidase in Manganese-Deficient Cells and Mice. (2018). https://pubmed.ncbi.nlm.nih.gov/29398562/ DOI: 10.1016/j.chembiol.2018.01.007

tissue_or_cell_type

Liver Sod2

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 508–519

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified SOD2, SOD2-overexpressing human cells, and dietary C57BL/6J mouse experiments · source_derived_draft · unverified_draft

### mn-enz-mouse-low-mn-iron-sod2 Mice fed the lower-manganese diet for four weeks had approximately 30% of isolated liver Sod2 iron-loaded, versus negligible iron loading in controls. Condition category: nutrient_deficiency nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Lower dietary manganese relative to iron changed liver Sod2 metal loading in mice. organism: Mus musculus tissue_or_cell_type: Liver Sod2 experimental_model: Purified SOD2, SOD2-overexpressing human cells, and dietary C57BL/6J mouse experiments limitations: Primary experimental scope only; no human dietary threshold, clinical treatment rule, or universal metal substitution is established. exposure: Four weeks of 40 ppm Mn/275 ppm Fe versus 150 ppm Mn/275 ppm Fe control. cross_nutrient: Dietary Mn:Fe balance affected mouse Sod2 metal occupancy. [mn-enz-29398562] Switch of Mitochondrial Superoxide Dismutase into a Prooxidant Peroxidase in Manganese-Deficient Cells and Mice. (2018). https://pubmed.ncbi.nlm.nih.gov/29398562/ DOI: 10.1016/j.chembiol.2018.01.007

cross_nutrient

Iron misincorporation competes with normal Mn cofactor chemistry; iron-loaded SOD2 is not functional replacement.

experimental_model

Purified SOD2, SOD2-overexpressing human cells, and dietary C57BL/6J mouse experiments

exposure

Enzyme metal substitution; low Mn:Fe cell media; altered mouse diets

limitations

Iron-loading experiments and overexpression cell models; no human prevalence or dietary threshold inferred.

nutrient_topic

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

organism

Homo sapiens; Mus musculus

plain_language

Iron in the SOD2 site can change what the enzyme does.

primary_references

[mn-enz-29398562] Switch of Mitochondrial Superoxide Dismutase into a Prooxidant Peroxidase in Manganese-Deficient Cells and Mice. (2018). https://pubmed.ncbi.nlm.nih.gov/29398562/ DOI: 10.1016/j.chembiol.2018.01.007

tissue_or_cell_type

Purified enzyme, cultured cells and mouse liver

Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 495–506

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified SOD2, SOD2-overexpressing human cells, and dietary C57BL/6J mouse experiments · source_derived_draft · unverified_draft

### mn-enz-sod2-iron-peroxidase Iron incorporation into SOD2 generated a form that used hydrogen peroxide for prooxidant peroxidase chemistry in the reported biochemical and cell experiments. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Iron in the SOD2 site can change what the enzyme does. organism: Homo sapiens; Mus musculus tissue_or_cell_type: Purified enzyme, cultured cells and mouse liver experimental_model: Purified SOD2, SOD2-overexpressing human cells, and dietary C57BL/6J mouse experiments limitations: Iron-loading experiments and overexpression cell models; no human prevalence or dietary threshold inferred. exposure: Enzyme metal substitution; low Mn:Fe cell media; altered mouse diets cross_nutrient: Iron misincorporation competes with normal Mn cofactor chemistry; iron-loaded SOD2 is not functional replacement. [mn-enz-29398562] Switch of Mitochondrial Superoxide Dismutase into a Prooxidant Peroxidase in Manganese-Deficient Cells and Mice. (2018). https://pubmed.ncbi.nlm.nih.gov/29398562/ DOI: 10.1016/j.chembiol.2018.01.007

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 volunteers with mild hyperlipidemia

limitations

A small baseline-comparison study cannot establish deficiency, iron depletion, or a causal nutrient interaction without controlled replication.

nutrient_topic

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

organism

Fourteen volunteers with mild hyperlipidemia

plain_language

During the same 45 mg/day trial, serum and red-cell folate and serum ferritin fell at weeks 4 and 8, while serum iron remained stable.

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

Nutrient and iron-status markers

Hydroxytyrosol: mechanism of action and interactions (2026-09-20) · lines 110–119

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 volunteers with mild hyperlipidemia · source_derived_draft · unverified_draft

## hydroxytyrosol-folate-ferritin During the same 45 mg/day trial, serum and red-cell folate and serum ferritin fell at weeks 4 and 8, while serum iron remained stable. Model/species: Fourteen volunteers with mild hyperlipidemia Tissue/system: Nutrient and iron-status markers Exposure: Purified hydroxytyrosol 45 mg/day Route: Oral Duration: 8 weeks Limits: A small baseline-comparison study cannot establish deficiency, iron depletion, or a causal nutrient interaction without controlled replication. 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

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

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

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

evidence_span

{"source_cache": "artifacts/pectin-research/6307932.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "fd45607a7ff1d1a20dd52d145134da591847919c3db47ef8a8cf5693fb9f80a1", "start_char": 0, "end_char": 1593, "text_sha256": "fd45607a7ff1d1a20dd52d145134da591847919c3db47ef8a8cf5693fb9f80a1"}

experimental_model

Within-person ileostomy balance study; six participants

exposure

15 g/day citrus pectin on days 5-7 of a 10-day low-fiber feeding protocol

limitations

Ileal apparent absorption and output are not whole-body status or clinical deficiency; the colon was bypassed.

nutrient_topic

Pectin research collection; topical membership is not evidence of a direct dietary effect. · Pectin, structurally heterogeneous plant polysaccharides

organism

Homo sapiens

plain_language

Less iron disappeared before the end of the small intestine.

primary_references

[pectin-p6307932] The effect of citrus pectin on the absorption of nutrients in the small intestine. (1983). https://pubmed.ncbi.nlm.nih.gov/6307932/

tissue_or_cell_type

Small intestine; ileal effluent

Pectin: metabolism, signaling and nutrient connections (2026-09-17) · lines 542–553

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Within-person ileostomy balance study; six participants · source_derived_draft · unverified_draft

### pectin-ileal-iron Apparent iron absorption fell in this ileostomy experiment. Condition category: normal nutrient_topic: Pectin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Less iron disappeared before the end of the small intestine. organism: Homo sapiens tissue_or_cell_type: Small intestine; ileal effluent experimental_model: Within-person ileostomy balance study; six participants limitations: Ileal apparent absorption and output are not whole-body status or clinical deficiency; the colon was bypassed. exposure: 15 g/day citrus pectin on days 5-7 of a 10-day low-fiber feeding protocol evidence_span: {"source_cache": "artifacts/pectin-research/6307932.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "fd45607a7ff1d1a20dd52d145134da591847919c3db47ef8a8cf5693fb9f80a1", "start_char": 0, "end_char": 1593, "text_sha256": "fd45607a7ff1d1a20dd52d145134da591847919c3db47ef8a8cf5693fb9f80a1"} [pectin-p6307932] The effect of citrus pectin on the absorption of nutrients in the small intestine. (1983). https://pubmed.ncbi.nlm.nih.gov/6307932/

evidence_span

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experimental_model

Tracer study in idiopathic hemochromatosis with in-vitro binding comparison

exposure

13 patients: pectin in eight, cellulose in five; 9 g/m2, own fasting controls; seven healthy basal comparators

limitations

Disease-specific small experiment; not a treatment recommendation or a universal effect of all fruit.

nutrient_topic

Pectin research collection; topical membership is not evidence of a direct dietary effect. · Pectin, structurally heterogeneous plant polysaccharides

organism

Homo sapiens; cell-free binding assay separately scoped

plain_language

Pectin can lower absorbed iron under these tested conditions.

primary_references

[pectin-p6247906] Evidence and mechanism for pectin-reduced intestinal inorganic iron absorption in idiopathic hemochromatosis. (1980). https://pubmed.ncbi.nlm.nih.gov/6247906/ DOI: 10.1093/ajcn/33.6.1225

tissue_or_cell_type

Intestinal inorganic iron absorption

Pectin: metabolism, signaling and nutrient connections (2026-09-17) · lines 633–644

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Tracer study in idiopathic hemochromatosis with in-vitro binding comparison · source_derived_draft · unverified_draft

### pectin-iron-absorption Pectin reduced inorganic iron fractional absorption in the hemochromatosis group, whereas cellulose did not show the same result. Condition category: normal nutrient_topic: Pectin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Pectin can lower absorbed iron under these tested conditions. organism: Homo sapiens; cell-free binding assay separately scoped tissue_or_cell_type: Intestinal inorganic iron absorption experimental_model: Tracer study in idiopathic hemochromatosis with in-vitro binding comparison limitations: Disease-specific small experiment; not a treatment recommendation or a universal effect of all fruit. exposure: 13 patients: pectin in eight, cellulose in five; 9 g/m2, own fasting controls; seven healthy basal comparators evidence_span: {"source_cache": "artifacts/pectin-research/6247906.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2c107283e705511284aaecb49a765185e48f825963c872c6306d76f9cf4565cf", "start_char": 0, "end_char": 1307, "text_sha256": "2c107283e705511284aaecb49a765185e48f825963c872c6306d76f9cf4565cf"} [pectin-p6247906] Evidence and mechanism for pectin-reduced intestinal inorganic iron absorption in idiopathic hemochromatosis. (1980). https://pubmed.ncbi.nlm.nih.gov/6247906/ DOI: 10.1093/ajcn/33.6.1225

evidence_span

{"source_cache": "artifacts/pectin-research/6247906.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2c107283e705511284aaecb49a765185e48f825963c872c6306d76f9cf4565cf", "start_char": 0, "end_char": 1307, "text_sha256": "2c107283e705511284aaecb49a765185e48f825963c872c6306d76f9cf4565cf"}

experimental_model

Tracer study in idiopathic hemochromatosis with in-vitro binding comparison

exposure

13 patients: pectin in eight, cellulose in five; 9 g/m2, own fasting controls; seven healthy basal comparators

limitations

Disease-specific small experiment; not a treatment recommendation or a universal effect of all fruit.

nutrient_topic

Pectin research collection; topical membership is not evidence of a direct dietary effect. · Pectin, structurally heterogeneous plant polysaccharides

organism

Cell-free assay

plain_language

Binding provides a candidate explanation for the absorption finding.

primary_references

[pectin-p6247906] Evidence and mechanism for pectin-reduced intestinal inorganic iron absorption in idiopathic hemochromatosis. (1980). https://pubmed.ncbi.nlm.nih.gov/6247906/ DOI: 10.1093/ajcn/33.6.1225

tissue_or_cell_type

In-vitro binding system

Pectin: metabolism, signaling and nutrient connections (2026-09-17) · lines 646–657

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Tracer study in idiopathic hemochromatosis with in-vitro binding comparison · source_derived_draft · unverified_draft

### pectin-iron-complex In-vitro pectin iron-binding capacity increased with pectin exposure; cellulose lacked the comparable binding response. Condition category: normal nutrient_topic: Pectin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Binding provides a candidate explanation for the absorption finding. organism: Cell-free assay tissue_or_cell_type: In-vitro binding system experimental_model: Tracer study in idiopathic hemochromatosis with in-vitro binding comparison limitations: Disease-specific small experiment; not a treatment recommendation or a universal effect of all fruit. exposure: 13 patients: pectin in eight, cellulose in five; 9 g/m2, own fasting controls; seven healthy basal comparators evidence_span: {"source_cache": "artifacts/pectin-research/6247906.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2c107283e705511284aaecb49a765185e48f825963c872c6306d76f9cf4565cf", "start_char": 0, "end_char": 1307, "text_sha256": "2c107283e705511284aaecb49a765185e48f825963c872c6306d76f9cf4565cf"} [pectin-p6247906] Evidence and mechanism for pectin-reduced intestinal inorganic iron absorption in idiopathic hemochromatosis. (1980). https://pubmed.ncbi.nlm.nih.gov/6247906/ DOI: 10.1093/ajcn/33.6.1225

evidence_span

{"source_cache": "artifacts/molybdenum-research/17135237.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3ccd6f2de98887d17d935999238a88d8901fe8a66bb9b48c9cbd5d179bf180d6", "start_char": 0, "end_char": 1343, "text_sha256": "3ccd6f2de98887d17d935999238a88d8901fe8a66bb9b48c9cbd5d179bf180d6"}

experimental_model

Purified human CDO1 crystallography, substrate binding, metal analysis and mutants

exposure

L-cysteine oxidation with molecular oxygen

limitations

The overall reaction and iron requirement are recorded; disputed detailed structural intermediates are not assigned as settled.

nutrient_topic

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

organism

Homo sapiens

plain_language

Iron-dependent CDO1 starts an upstream sulfur-breakdown route.

primary_references

[mo-p17135237] An insight into the mechanism of human cysteine dioxygenase. Key roles of the thioether-bonded tyrosine-cysteine cofactor. (2007). https://pubmed.ncbi.nlm.nih.gov/17135237/ DOI: 10.1074/jbc.m609337200

tissue_or_cell_type

Recombinant human cysteine dioxygenase

Molybdenum: cofactor assembly, sulfur metabolism and nutrient interactions (2026-09-17) · lines 677–688

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human CDO1 crystallography, substrate binding, metal analysis and mutants · source_derived_draft · unverified_draft

### mo-cdo-csa Human CDO1 oxidizes cysteine to cysteine sulfinic acid using molecular oxygen and a non-heme iron center. Condition category: normal nutrient_topic: Molybdenum research collection; topical membership is not evidence of a direct dietary effect. plain_language: Iron-dependent CDO1 starts an upstream sulfur-breakdown route. organism: Homo sapiens tissue_or_cell_type: Recombinant human cysteine dioxygenase experimental_model: Purified human CDO1 crystallography, substrate binding, metal analysis and mutants limitations: The overall reaction and iron requirement are recorded; disputed detailed structural intermediates are not assigned as settled. exposure: L-cysteine oxidation with molecular oxygen evidence_span: {"source_cache": "artifacts/molybdenum-research/17135237.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3ccd6f2de98887d17d935999238a88d8901fe8a66bb9b48c9cbd5d179bf180d6", "start_char": 0, "end_char": 1343, "text_sha256": "3ccd6f2de98887d17d935999238a88d8901fe8a66bb9b48c9cbd5d179bf180d6"} [mo-p17135237] An insight into the mechanism of human cysteine dioxygenase. Key roles of the thioether-bonded tyrosine-cysteine cofactor. (2007). https://pubmed.ncbi.nlm.nih.gov/17135237/ DOI: 10.1074/jbc.m609337200

evidence_span

{"source_cache": "artifacts/molybdenum-research/23703616.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9034da6c790ca6e0c60dd765eec631ea2875c6caf65f6d15d59733bc5e0ee0ec", "start_char": 0, "end_char": 1596, "text_sha256": "9034da6c790ca6e0c60dd765eec631ea2875c6caf65f6d15d59733bc5e0ee0ec"}

experimental_model

Human-cell siRNA plus recombinant cytochrome-b5/cofactor reconstitution

exposure

mARC, CYB5B and CYB5A depletion; apo-CYB5

limitations

Expression-dependent cellular contributions; no clinical iron or B2 supplementation test.

nutrient_topic

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

organism

Homo sapiens; separate mouse Cyb5a knockout

plain_language

Removing the iron-containing heme breaks this electron-transfer step.

primary_references

[mo-p23703616] The involvement of mitochondrial amidoxime reducing components 1 and 2 and mitochondrial cytochrome b5 in N-reductive metabolism in human cells. (2013). https://pubmed.ncbi.nlm.nih.gov/23703616/ DOI: 10.1074/jbc.m113.474916

tissue_or_cell_type

HEK293 and second human cell line; purified proteins

Molybdenum: cofactor assembly, sulfur metabolism and nutrient interactions (2026-09-17) · lines 1002–1013

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human-cell siRNA plus recombinant cytochrome-b5/cofactor reconstitution · source_derived_draft · unverified_draft

### mo-cyb5b-heme Heme-free apo-CYB5 failed to support N-reduction in the reconstituted system. Condition category: normal nutrient_topic: Molybdenum research collection; topical membership is not evidence of a direct dietary effect. plain_language: Removing the iron-containing heme breaks this electron-transfer step. organism: Homo sapiens; separate mouse Cyb5a knockout tissue_or_cell_type: HEK293 and second human cell line; purified proteins experimental_model: Human-cell siRNA plus recombinant cytochrome-b5/cofactor reconstitution limitations: Expression-dependent cellular contributions; no clinical iron or B2 supplementation test. exposure: mARC, CYB5B and CYB5A depletion; apo-CYB5 evidence_span: {"source_cache": "artifacts/molybdenum-research/23703616.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9034da6c790ca6e0c60dd765eec631ea2875c6caf65f6d15d59733bc5e0ee0ec", "start_char": 0, "end_char": 1596, "text_sha256": "9034da6c790ca6e0c60dd765eec631ea2875c6caf65f6d15d59733bc5e0ee0ec"} [mo-p23703616] The involvement of mitochondrial amidoxime reducing components 1 and 2 and mitochondrial cytochrome b5 in N-reductive metabolism in human cells. (2013). https://pubmed.ncbi.nlm.nih.gov/23703616/ DOI: 10.1074/jbc.m113.474916

evidence_span

{"source_cache": "artifacts/molybdenum-research/15180982.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "722c11f1c29a720fb7105f37962af2652ce95b6734afdb59d675dee0b8302097", "start_char": 0, "end_char": 1828, "text_sha256": "722c11f1c29a720fb7105f37962af2652ce95b6734afdb59d675dee0b8302097"}

experimental_model

Recombinant human MOCS1A, cysteine mutagenesis and multiple spectroscopic methods

exposure

Aerobic versus anaerobic purification; iron-sulfur reconstitution

limitations

Cluster states depend on preparation and oxygen exposure; the paper does not demonstrate a dietary iron or methyl-donor threshold.

nutrient_topic

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

organism

Human protein expressed in Escherichia coli

plain_language

Molybdenum-cofactor assembly itself requires iron-sulfur machinery.

primary_references

[mo-p15180982] Characterization of MOCS1A, an oxygen-sensitive iron-sulfur protein involved in human molybdenum cofactor biosynthesis. (2004). https://pubmed.ncbi.nlm.nih.gov/15180982/ DOI: 10.1074/jbc.m313398200

tissue_or_cell_type

Purified protein and bacterial complementation

Molybdenum: cofactor assembly, sulfur metabolism and nutrient interactions (2026-09-17) · lines 313–324

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human MOCS1A, cysteine mutagenesis and multiple spectroscopic methods · source_derived_draft · unverified_draft

### mo-mocs1a-fes Anaerobic reconstitution yielded human MOCS1A containing two [4Fe-4S] clusters. Condition category: normal nutrient_topic: Molybdenum research collection; topical membership is not evidence of a direct dietary effect. plain_language: Molybdenum-cofactor assembly itself requires iron-sulfur machinery. organism: Human protein expressed in Escherichia coli tissue_or_cell_type: Purified protein and bacterial complementation experimental_model: Recombinant human MOCS1A, cysteine mutagenesis and multiple spectroscopic methods limitations: Cluster states depend on preparation and oxygen exposure; the paper does not demonstrate a dietary iron or methyl-donor threshold. exposure: Aerobic versus anaerobic purification; iron-sulfur reconstitution evidence_span: {"source_cache": "artifacts/molybdenum-research/15180982.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "722c11f1c29a720fb7105f37962af2652ce95b6734afdb59d675dee0b8302097", "start_char": 0, "end_char": 1828, "text_sha256": "722c11f1c29a720fb7105f37962af2652ce95b6734afdb59d675dee0b8302097"} [mo-p15180982] Characterization of MOCS1A, an oxygen-sensitive iron-sulfur protein involved in human molybdenum cofactor biosynthesis. (2004). https://pubmed.ncbi.nlm.nih.gov/15180982/ DOI: 10.1074/jbc.m313398200

evidence_span

{"source_cache": "artifacts/molybdenum-research/31127934.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d0efd64e9cde371d0223d63607f5f6b76aada3a628c526f915d9b306c9bef7de", "start_char": 0, "end_char": 1649, "text_sha256": "d0efd64e9cde371d0223d63607f5f6b76aada3a628c526f915d9b306c9bef7de"}

experimental_model

Human SUOX Gly362Ser patient fibroblasts and recombinant enzyme maturation assays

exposure

G362S versus WT protein; Moco reconstitution and molybdate supplementation in culture

limitations

One genotype; in-vitro molybdate rescue is not demonstrated clinical treatment for all SUOX defects.

nutrient_topic

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

organism

Homo sapiens

plain_language

Molybdenum and iron-containing heme perform different jobs within this enzyme.

primary_references

[mo-p31127934] Impaired mitochondrial maturation of sulfite oxidase in a patient with severe sulfite oxidase deficiency. (2019). https://pubmed.ncbi.nlm.nih.gov/31127934/ DOI: 10.1093/hmg/ddz109

tissue_or_cell_type

Mitochondrial intermembrane space; patient fibroblasts

Molybdenum: cofactor assembly, sulfur metabolism and nutrient interactions (2026-09-17) · lines 599–610

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human SUOX Gly362Ser patient fibroblasts and recombinant enzyme maturation assays · source_derived_draft · unverified_draft

### mo-suox-cofactors SUOX sulfite oxidation depends on Moco at the catalytic site and a separate heme cofactor. Condition category: normal nutrient_topic: Molybdenum research collection; topical membership is not evidence of a direct dietary effect. plain_language: Molybdenum and iron-containing heme perform different jobs within this enzyme. organism: Homo sapiens tissue_or_cell_type: Mitochondrial intermembrane space; patient fibroblasts experimental_model: Human SUOX Gly362Ser patient fibroblasts and recombinant enzyme maturation assays limitations: One genotype; in-vitro molybdate rescue is not demonstrated clinical treatment for all SUOX defects. exposure: G362S versus WT protein; Moco reconstitution and molybdate supplementation in culture evidence_span: {"source_cache": "artifacts/molybdenum-research/31127934.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d0efd64e9cde371d0223d63607f5f6b76aada3a628c526f915d9b306c9bef7de", "start_char": 0, "end_char": 1649, "text_sha256": "d0efd64e9cde371d0223d63607f5f6b76aada3a628c526f915d9b306c9bef7de"} [mo-p31127934] Impaired mitochondrial maturation of sulfite oxidase in a patient with severe sulfite oxidase deficiency. (2019). https://pubmed.ncbi.nlm.nih.gov/31127934/ DOI: 10.1093/hmg/ddz109

availability_state

nutrient_deficiency Imported condition classification; unverified.

experimental_model

Renal gene-expression assay.

limitations

Does not by itself measure circulating EPO or prove ineffective erythropoiesis mediation.

nutrient_topic

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

organism

Rattus norvegicus

plain_language

A shortage affected expression of an erythropoietic signal.

primary_references

[va-cunha2014] Vitamin A deficiency modulates iron metabolism via ineffective erythropoiesis (2014). https://pubmed.ncbi.nlm.nih.gov/24998947/ DOI: 10.1016/j.jnutbio.2014.05.005

tissue_or_cell_type

Kidney

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1755–1764

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Renal gene-expression assay. · source_derived_draft · unverified_draft

### va-deficiency-epo-transcript Vitamin A deficiency reduced renal Epo mRNA in the rat experiment. Condition category: nutrient_deficiency nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: A shortage affected expression of an erythropoietic signal. organism: Rattus norvegicus tissue_or_cell_type: Kidney experimental_model: Renal gene-expression assay. limitations: Does not by itself measure circulating EPO or prove ineffective erythropoiesis mediation. [va-cunha2014] Vitamin A deficiency modulates iron metabolism via ineffective erythropoiesis (2014). https://pubmed.ncbi.nlm.nih.gov/24998947/ DOI: 10.1016/j.jnutbio.2014.05.005

availability_state

nutrient_deficiency Imported condition classification; unverified.

experimental_model

Intestinal mRNA assay.

limitations

Does not quantify ferroportin membrane protein or iron-export flux.

nutrient_topic

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

organism

Rattus norvegicus

plain_language

Expression of an iron-export component changed alongside systemic signals.

primary_references

[va-cunha2016] Vitamin A deficiency modulates iron metabolism independent of hemojuvelin (Hfe2) and bone morphogenetic protein 6 (Bmp6) transcript levels (2016). https://pubmed.ncbi.nlm.nih.gov/27551308/ DOI: 10.1186/s12263-016-0519-4

tissue_or_cell_type

Small intestine

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1778–1787

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Intestinal mRNA assay. · source_derived_draft · unverified_draft

### va-deficiency-ferroportin-transcript Vitamin A deficiency reduced intestinal Fpn1 transcripts in the same rat study. Condition category: nutrient_deficiency nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Expression of an iron-export component changed alongside systemic signals. organism: Rattus norvegicus tissue_or_cell_type: Small intestine experimental_model: Intestinal mRNA assay. limitations: Does not quantify ferroportin membrane protein or iron-export flux. [va-cunha2016] Vitamin A deficiency modulates iron metabolism independent of hemojuvelin (Hfe2) and bone morphogenetic protein 6 (Bmp6) transcript levels (2016). https://pubmed.ncbi.nlm.nih.gov/27551308/ DOI: 10.1186/s12263-016-0519-4

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Vitamin A deficiency -> iron distribution.

experimental_model

Controlled rat dietary groups.

limitations

Erythrophagocytosis is a proposed explanation, not a fully isolated causal sequence.

nutrient_topic

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

organism

Rattus norvegicus

plain_language

Iron could be retained in one tissue while circulating availability fell.

primary_references

[va-cunha2014] Vitamin A deficiency modulates iron metabolism via ineffective erythropoiesis (2014). https://pubmed.ncbi.nlm.nih.gov/24998947/ DOI: 10.1016/j.jnutbio.2014.05.005

tissue_or_cell_type

Spleen and serum

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Vitamin A: forms, mechanisms, deficiency and excess (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 · Controlled rat dietary groups. · source_derived_draft · unverified_draft

### va-deficiency-iron-sequestration Vitamin A-deficient rats had more splenic iron but lower serum iron and transferrin saturation. Condition category: nutrient_deficiency nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Iron could be retained in one tissue while circulating availability fell. organism: Rattus norvegicus tissue_or_cell_type: Spleen and serum experimental_model: Controlled rat dietary groups. limitations: Erythrophagocytosis is a proposed explanation, not a fully isolated causal sequence. cross_nutrient: Vitamin A deficiency -> iron distribution. [va-cunha2014] Vitamin A deficiency modulates iron metabolism via ineffective erythropoiesis (2014). https://pubmed.ncbi.nlm.nih.gov/24998947/ DOI: 10.1016/j.jnutbio.2014.05.005

cross_nutrient

Vitamin A/iron absorption replication disagreement.

experimental_model

Water/coffee meal conditions; stable and radioisotope methods.

limitations

Possible effect modification by poor vitamin A status remained unresolved; beta-carotene was not directly retested.

nutrient_topic

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

organism

Homo sapiens

plain_language

Follow-up experiments did not reproduce the earlier positive result.

primary_references

[va-walczyk2003] No enhancing effect of vitamin A on iron absorption in humans (2003). https://pubmed.ncbi.nlm.nih.gov/12499334/ DOI: 10.1093/ajcn/77.1.144

tissue_or_cell_type

Intestinal absorption

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1566–1576

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Water/coffee meal conditions; stable and radioisotope methods. · source_derived_draft · unverified_draft

### va-iron-absorption-no-enhancement2003 Five isotope studies did not confirm enhanced iron absorption after adding retinyl palmitate to corn-bread meals. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Follow-up experiments did not reproduce the earlier positive result. organism: Homo sapiens tissue_or_cell_type: Intestinal absorption experimental_model: Water/coffee meal conditions; stable and radioisotope methods. limitations: Possible effect modification by poor vitamin A status remained unresolved; beta-carotene was not directly retested. cross_nutrient: Vitamin A/iron absorption replication disagreement. [va-walczyk2003] No enhancing effect of vitamin A on iron absorption in humans (2003). https://pubmed.ncbi.nlm.nih.gov/12499334/ DOI: 10.1093/ajcn/77.1.144

cross_nutrient

Vitamin A/carotene -> iron absorption; contested.

experimental_model

Six human cereal-meal studies.

limitations

Not consistently replicated; the claimed iron-complex mechanism was proposed rather than structurally demonstrated.

nutrient_topic

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

organism

Homo sapiens

plain_language

This study found that the meal additives made more iron available.

primary_references

[va-garciacasal1998] Vitamin A and beta-carotene can improve nonheme iron absorption from rice, wheat and corn by humans (1998). https://pubmed.ncbi.nlm.nih.gov/9482776/ DOI: 10.1093/jn/128.3.646

tissue_or_cell_type

Intestinal absorption

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1542–1552

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Six human cereal-meal studies. · source_derived_draft · unverified_draft

### va-iron-absorption-positive1998 Vitamin A and beta-carotene increased labelled nonheme iron absorption from tested cereal meals. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: This study found that the meal additives made more iron available. organism: Homo sapiens tissue_or_cell_type: Intestinal absorption experimental_model: Six human cereal-meal studies. limitations: Not consistently replicated; the claimed iron-complex mechanism was proposed rather than structurally demonstrated. cross_nutrient: Vitamin A/carotene -> iron absorption; contested. [va-garciacasal1998] Vitamin A and beta-carotene can improve nonheme iron absorption from rice, wheat and corn by humans (1998). https://pubmed.ncbi.nlm.nih.gov/9482776/ DOI: 10.1093/jn/128.3.646

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

Iron availability supports provitamin A cleavage in this in vitro model.

evidence_location

Abstract

experimental_model

Human small-intestinal mucosa and Caco-2 TC7 cells; desferrioxamine and iron addition.

exposure

Increasing desferrioxamine concentrations.

limitations

Drug-induced chelation; BCO1 protein abundance and human dietary deficiency were not directly established.

nutrient_topic

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

organism

Homo sapiens

outcome

Desferrioxamine reduced beta-carotene-cleaving activity in human intestinal mucosa and TC7 cells.

plain_language

Sequestering iron limited conversion of provitamin A to retinal.

primary_references

[va-during-2001] beta-Carotene 15,15'-Dioxygenase activity in human tissues and cells: evidence of an iron dependency (2001). https://pubmed.ncbi.nlm.nih.gov/12031257/ DOI: 10.1016/S0955-2863(01)00184-X

tissue_or_cell_type

Small-intestinal mucosa and Caco-2 TC7 cells

trigger_kind

machinery_impairment Imported condition classification; unverified.

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 187–200

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human small-intestinal mucosa and Caco-2 TC7 cells; desferrioxamine and iron addition. · source_derived_draft · unverified_draft

### va-iron-chelation-cleavage Desferrioxamine reduced beta-carotene-cleaving activity in human intestinal mucosa and TC7 cells. Condition category: machinery_impairment nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Sequestering iron limited conversion of provitamin A to retinal. organism: Homo sapiens tissue_or_cell_type: Small-intestinal mucosa and Caco-2 TC7 cells experimental_model: Human small-intestinal mucosa and Caco-2 TC7 cells; desferrioxamine and iron addition. limitations: Drug-induced chelation; BCO1 protein abundance and human dietary deficiency were not directly established. exposure: Increasing desferrioxamine concentrations. outcome: Desferrioxamine reduced beta-carotene-cleaving activity in human intestinal mucosa and TC7 cells. evidence_location: Abstract cross_nutrient: Iron availability supports provitamin A cleavage in this in vitro model. [va-during-2001] beta-Carotene 15,15'-Dioxygenase activity in human tissues and cells: evidence of an iron dependency (2001). https://pubmed.ncbi.nlm.nih.gov/12031257/ DOI: 10.1016/S0955-2863(01)00184-X

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Vitamin A/iron -> hemoglobin response.

experimental_model

Eight-week randomized trial.

limitations

Combined benefit does not prove a biochemical synergy or specify the cellular mediator.

nutrient_topic

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

organism

Homo sapiens

plain_language

Correcting more than one shortage improved the measured response in this population.

primary_references

[va-suharno1993] Supplementation with vitamin A and iron for nutritional anaemia in pregnant women in West Java, Indonesia (1993). https://pubmed.ncbi.nlm.nih.gov/7901636/ DOI: 10.1016/0140-6736(93)92246-p

tissue_or_cell_type

Blood

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1448–1458

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Eight-week randomized trial. · source_derived_draft · unverified_draft

### va-iron-combined-hemoglobin Combined vitamin A and iron produced the largest hemoglobin response in the factorial pregnancy trial. Condition category: nutrient_deficiency nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Correcting more than one shortage improved the measured response in this population. organism: Homo sapiens tissue_or_cell_type: Blood experimental_model: Eight-week randomized trial. limitations: Combined benefit does not prove a biochemical synergy or specify the cellular mediator. cross_nutrient: Vitamin A/iron -> hemoglobin response. [va-suharno1993] Supplementation with vitamin A and iron for nutritional anaemia in pregnant women in West Java, Indonesia (1993). https://pubmed.ncbi.nlm.nih.gov/7901636/ DOI: 10.1016/0140-6736(93)92246-p

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Vitamin A -> EPO/iron use.

experimental_model

Randomized ten-month follow-up.

limitations

EPO was measured, not blocked; its mediation of the hemoglobin response remains inferred.

nutrient_topic

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

organism

Homo sapiens

plain_language

Vitamin A can influence the signal that supports red-cell production.

primary_references

[va-zimmermann2006-iron] Vitamin A supplementation in children with poor vitamin A and iron status increases erythropoietin and hemoglobin concentrations without changing total body iron (2006). https://pubmed.ncbi.nlm.nih.gov/16960172/ DOI: 10.1093/ajcn/84.3.580

tissue_or_cell_type

Blood

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1460–1470

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized ten-month follow-up. · source_derived_draft · unverified_draft

### va-repletion-erythropoietin Vitamin A increased circulating EPO and hemoglobin in schoolchildren with poor nutrient status. Condition category: nutrient_deficiency nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin A can influence the signal that supports red-cell production. organism: Homo sapiens tissue_or_cell_type: Blood experimental_model: Randomized ten-month follow-up. limitations: EPO was measured, not blocked; its mediation of the hemoglobin response remains inferred. cross_nutrient: Vitamin A -> EPO/iron use. [va-zimmermann2006-iron] Vitamin A supplementation in children with poor vitamin A and iron status increases erythropoietin and hemoglobin concentrations without changing total body iron (2006). https://pubmed.ncbi.nlm.nih.gov/16960172/ DOI: 10.1093/ajcn/84.3.580

availability_state

nutrient_deficiency Imported condition classification; unverified.

experimental_model

Ferritin/transferrin-receptor-based estimates.

limitations

Redistribution is an interpretation; liver iron was not directly biopsied.

nutrient_topic

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

organism

Homo sapiens

plain_language

A better blood count did not require a measured increase in total-body iron.

primary_references

[va-zimmermann2006-iron] Vitamin A supplementation in children with poor vitamin A and iron status increases erythropoietin and hemoglobin concentrations without changing total body iron (2006). https://pubmed.ncbi.nlm.nih.gov/16960172/ DOI: 10.1093/ajcn/84.3.580

tissue_or_cell_type

Blood; inferred storage

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1472–1481

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ferritin/transferrin-receptor-based estimates. · source_derived_draft · unverified_draft

### va-repletion-iron-store-redistribution Ferritin fell while calculated total-body iron remained unchanged in the same trial, consistent with redistribution of existing iron. Condition category: nutrient_deficiency nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: A better blood count did not require a measured increase in total-body iron. organism: Homo sapiens tissue_or_cell_type: Blood; inferred storage experimental_model: Ferritin/transferrin-receptor-based estimates. limitations: Redistribution is an interpretation; liver iron was not directly biopsied. [va-zimmermann2006-iron] Vitamin A supplementation in children with poor vitamin A and iron status increases erythropoietin and hemoglobin concentrations without changing total body iron (2006). https://pubmed.ncbi.nlm.nih.gov/16960172/ DOI: 10.1093/ajcn/84.3.580

cross_nutrient

true

evidence_location

Primary abstract

experimental_model

Microsomes and Triton-dispersed lipid micelles

exposure

Iron-dependent peroxidation; physiological vitamin E:phospholipid ratio as reported in abstract.

limitations

Exact concentrations are not available in the inspected abstract. Model-specific dependence does not imply every membrane requires added GPX4 to show E protection.

nutrient_topic

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

organism

Rattus norvegicus

plain_language

Vitamin E protection depended on peroxide removal by the GPX4/glutathione system in these preparations.

primary_references

[ver-maiorino1989] Microsomal lipid peroxidation: effect of vitamin E and its functional interaction with phospholipid hydroperoxide glutathione peroxidase. (1989). https://pubmed.ncbi.nlm.nih.gov/2586229/ DOI: 10.1007/bf02535211

tissue_or_cell_type

Liver microsomal lipids

Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 592–604

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Microsomes and Triton-dispersed lipid micelles · source_derived_draft · unverified_draft

### ver-gpx4-gsh-tocopherol-cooperation At a physiological vitamin E-to-phospholipid ratio, inhibition of iron-dependent lipid peroxidation in rat liver microsomes and dispersed microsomal lipids was observed only when PHGPX (GPX4) and glutathione were also present. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin E protection depended on peroxide removal by the GPX4/glutathione system in these preparations. organism: Rattus norvegicus tissue_or_cell_type: Liver microsomal lipids experimental_model: Microsomes and Triton-dispersed lipid micelles limitations: Exact concentrations are not available in the inspected abstract. Model-specific dependence does not imply every membrane requires added GPX4 to show E protection. exposure: Iron-dependent peroxidation; physiological vitamin E:phospholipid ratio as reported in abstract. cross_nutrient: true evidence_location: Primary abstract [ver-maiorino1989] Microsomal lipid peroxidation: effect of vitamin E and its functional interaction with phospholipid hydroperoxide glutathione peroxidase. (1989). https://pubmed.ncbi.nlm.nih.gov/2586229/ DOI: 10.1007/bf02535211

cross_nutrient

true

evidence_location

Primary abstract

experimental_model

Sequential peroxide reduction and iron challenge

exposure

Photoperoxidation → GSH/PHGPX → iron-dependent challenge.

limitations

Ascorbate participates in this deliberately pro-oxidizing assay; this is not evidence that normal vitamin C intake damages membranes.

nutrient_topic

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

organism

Human-derived cell-free membranes

plain_language

Removing membrane hydroperoxides prevented an iron-driven burst of further oxidation.

primary_references

[ver-thomas1990] Protective action of phospholipid hydroperoxide glutathione peroxidase against membrane-damaging lipid peroxidation. In situ reduction of phospholipid and cholesterol hydroperoxides. (1990). https://pubmed.ncbi.nlm.nih.gov/2294113/ DOI: 10.1016/s0021-9258(19)40252-4

tissue_or_cell_type

Erythrocyte ghosts

Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 578–590

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Sequential peroxide reduction and iron challenge · source_derived_draft · unverified_draft

### ver-peroxide-removal-iron-burst GSH/PHGPX pretreatment completely suppressed the subsequent radical-peroxidation burst when photooxidized erythrocyte ghosts were challenged with ascorbate/iron or xanthine/xanthine-oxidase/iron. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Removing membrane hydroperoxides prevented an iron-driven burst of further oxidation. organism: Human-derived cell-free membranes tissue_or_cell_type: Erythrocyte ghosts experimental_model: Sequential peroxide reduction and iron challenge limitations: Ascorbate participates in this deliberately pro-oxidizing assay; this is not evidence that normal vitamin C intake damages membranes. exposure: Photoperoxidation → GSH/PHGPX → iron-dependent challenge. cross_nutrient: true evidence_location: Primary abstract [ver-thomas1990] Protective action of phospholipid hydroperoxide glutathione peroxidase against membrane-damaging lipid peroxidation. In situ reduction of phospholipid and cholesterol hydroperoxides. (1990). https://pubmed.ncbi.nlm.nih.gov/2294113/ DOI: 10.1016/s0021-9258(19)40252-4

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_span

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experimental_model

Five-week factorial iron/copper feeding

exposure

Approximately 8800, 80 or 11 ppm iron crossed with approximately 183, 8 or 0.9 ppm copper

limitations

Very high experimental iron exposure; not an estimate of human supplement risk at ordinary intake. Copper restoration did not normalize every iron measure.

nutrient_topic

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

organism

Weanling male Sprague-Dawley rats

plain_language

Correcting the copper-related problem did not mean the excess-iron problem had disappeared.

primary_references

[iron-p27537180] High-Iron Consumption Impairs Growth and Causes Copper-Deficiency Anemia in Weanling Sprague-Dawley Rats. (2016). https://pubmed.ncbi.nlm.nih.gov/27537180/ DOI: 10.1371/journal.pone.0161033

tissue_or_cell_type

Systemic copper and iron status

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 927–938

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Five-week factorial iron/copper feeding · source_derived_draft · unverified_draft

### iron-copper-rescue-tradeoff Additional copper prevented the reported growth, cardiac and anemia disturbances under high-iron feeding, but increased hepatic nonheme iron loading. Condition category: nutrient_deficiency nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: Correcting the copper-related problem did not mean the excess-iron problem had disappeared. organism: Weanling male Sprague-Dawley rats tissue_or_cell_type: Systemic copper and iron status experimental_model: Five-week factorial iron/copper feeding limitations: Very high experimental iron exposure; not an estimate of human supplement risk at ordinary intake. Copper restoration did not normalize every iron measure. exposure: Approximately 8800, 80 or 11 ppm iron crossed with approximately 183, 8 or 0.9 ppm copper evidence_span: {"source_cache": "artifacts/iron-research/27537180.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "59f2a83f1bffcacfed0df109f3690413aa2e6f08be6ad400817c5cbe2165e523", "start_char": 0, "end_char": 1840, "text_sha256": "59f2a83f1bffcacfed0df109f3690413aa2e6f08be6ad400817c5cbe2165e523"} [iron-p27537180] High-Iron Consumption Impairs Growth and Causes Copper-Deficiency Anemia in Weanling Sprague-Dawley Rats. (2016). https://pubmed.ncbi.nlm.nih.gov/27537180/ DOI: 10.1371/journal.pone.0161033

evidence_span

{"source_cache": "artifacts/iron-research/15049686.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "76bcb8ae12316350b1161f32c1633e2b5c752fcbf7e158940385b354ee3452d2", "start_char": 0, "end_char": 1167, "text_sha256": "76bcb8ae12316350b1161f32c1633e2b5c752fcbf7e158940385b354ee3452d2"}

experimental_model

Product-bound human HO-1 structure

exposure

Biliverdin-bound structure compared with heme-bound enzyme

limitations

Product release interpretation from structure; no in-vivo flux measurement.

nutrient_topic

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

organism

Human enzyme

plain_language

Breaking open heme makes its iron available for reuse.

primary_references

[iron-p15049686] Crystal structure of human heme oxygenase-1 in a complex with biliverdin. (2004). https://pubmed.ncbi.nlm.nih.gov/15049686/ DOI: 10.1021/bi035451l

tissue_or_cell_type

Purified heme oxygenase-1

Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 576–587

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Product-bound human HO-1 structure · source_derived_draft · unverified_draft

### iron-heme-oxygenase Heme oxygenase oxidatively cleaves heme to biliverdin with release of iron and carbon monoxide. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: Breaking open heme makes its iron available for reuse. organism: Human enzyme tissue_or_cell_type: Purified heme oxygenase-1 experimental_model: Product-bound human HO-1 structure limitations: Product release interpretation from structure; no in-vivo flux measurement. exposure: Biliverdin-bound structure compared with heme-bound enzyme evidence_span: {"source_cache": "artifacts/iron-research/15049686.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "76bcb8ae12316350b1161f32c1633e2b5c752fcbf7e158940385b354ee3452d2", "start_char": 0, "end_char": 1167, "text_sha256": "76bcb8ae12316350b1161f32c1633e2b5c752fcbf7e158940385b354ee3452d2"} [iron-p15049686] Crystal structure of human heme oxygenase-1 in a complex with biliverdin. (2004). https://pubmed.ncbi.nlm.nih.gov/15049686/ DOI: 10.1021/bi035451l

evidence_span

{"source_cache": "artifacts/iron-research/15514116.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "00a292f6693116798182b0f9418f2eb8466aa029f32905019416422002158c4a", "start_char": 0, "end_char": 758, "text_sha256": "00a292f6693116798182b0f9418f2eb8466aa029f32905019416422002158c4a"}

experimental_model

Hepcidin binding and cellular export experiments

exposure

Hepcidin exposure

limitations

Post-translational export regulation; no dose-response to dietary iron is inferred from the cell experiment.

nutrient_topic

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

organism

Tissue-culture ferroportin systems

plain_language

Iron can be held inside cells instead of reaching the circulation.

primary_references

[iron-p15514116] Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. (2004). https://pubmed.ncbi.nlm.nih.gov/15514116/ DOI: 10.1126/science.1104742

tissue_or_cell_type

Plasma membrane

Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 732–743

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Hepcidin binding and cellular export experiments · source_derived_draft · unverified_draft

### iron-hepcidin-export Hepcidin-induced ferroportin removal reduced cellular iron export. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: Iron can be held inside cells instead of reaching the circulation. organism: Tissue-culture ferroportin systems tissue_or_cell_type: Plasma membrane experimental_model: Hepcidin binding and cellular export experiments limitations: Post-translational export regulation; no dose-response to dietary iron is inferred from the cell experiment. exposure: Hepcidin exposure evidence_span: {"source_cache": "artifacts/iron-research/15514116.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "00a292f6693116798182b0f9418f2eb8466aa029f32905019416422002158c4a", "start_char": 0, "end_char": 758, "text_sha256": "00a292f6693116798182b0f9418f2eb8466aa029f32905019416422002158c4a"} [iron-p15514116] Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. (2004). https://pubmed.ncbi.nlm.nih.gov/15514116/ DOI: 10.1126/science.1104742

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/iron-research/16439678.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ec63a88b5bebf3aecdfdea088979b051141b6ce89ceec92b66d219b99b6512c2", "start_char": 0, "end_char": 1003, "text_sha256": "ec63a88b5bebf3aecdfdea088979b051141b6ce89ceec92b66d219b99b6512c2"}

experimental_model

Human case with compound-heterozygous DMT1 variants

exposure

SLC11A2 V114 deletion and G212V variants

limitations

Rare genetic syndrome; ferritin is not a universal quantitative proxy for liver iron in this setting.

nutrient_topic

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

organism

Human patient, compared with two prior cases

plain_language

Having iron in the liver did not ensure that developing red cells could use it.

primary_references

[iron-p16439678] Two new human DMT1 gene mutations in a patient with microcytic anemia, low ferritinemia, and liver iron overload. (2006). https://pubmed.ncbi.nlm.nih.gov/16439678/ DOI: 10.1182/blood-2005-10-4269

tissue_or_cell_type

Red-cell indices, liver and blood markers

trigger_kind

machinery_impairment Imported condition classification; unverified.

Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 1031–1042

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human case with compound-heterozygous DMT1 variants · source_derived_draft · unverified_draft

### iron-human-dmt1-defect The patient had microcytic anemia from birth and progressive liver iron overload with compound-heterozygous DMT1 mutations. Condition category: machinery_impairment nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: Having iron in the liver did not ensure that developing red cells could use it. organism: Human patient, compared with two prior cases tissue_or_cell_type: Red-cell indices, liver and blood markers experimental_model: Human case with compound-heterozygous DMT1 variants limitations: Rare genetic syndrome; ferritin is not a universal quantitative proxy for liver iron in this setting. exposure: SLC11A2 V114 deletion and G212V variants evidence_span: {"source_cache": "artifacts/iron-research/16439678.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ec63a88b5bebf3aecdfdea088979b051141b6ce89ceec92b66d219b99b6512c2", "start_char": 0, "end_char": 1003, "text_sha256": "ec63a88b5bebf3aecdfdea088979b051141b6ce89ceec92b66d219b99b6512c2"} [iron-p16439678] Two new human DMT1 gene mutations in a patient with microcytic anemia, low ferritinemia, and liver iron overload. (2006). https://pubmed.ncbi.nlm.nih.gov/16439678/ DOI: 10.1182/blood-2005-10-4269

evidence_span

{"source_cache": "artifacts/iron-research/16373698.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0d3e9b3d6c8961f94af38195eab5b0b3180c321da1c7ca75ae956036a60b16cc", "start_char": 0, "end_char": 1165, "text_sha256": "0d3e9b3d6c8961f94af38195eab5b0b3180c321da1c7ca75ae956036a60b16cc"}

experimental_model

Mutagenesis, EPR and catalytic assays

exposure

Conserved tyrosine mutations around the diiron center

limitations

Purified enzyme mechanisms; no recommendation to increase dietary iron for DNA synthesis.

nutrient_topic

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

organism

Human RRM2 and RRM2B proteins

plain_language

DNA building-block synthesis needs a functioning iron/radical enzyme system.

primary_references

[iron-p16373698] A dityrosyl-diiron radical cofactor center is essential for human ribonucleotide reductases. (2005). https://pubmed.ncbi.nlm.nih.gov/16373698/ DOI: 10.1158/1535-7163.mct-05-0273

tissue_or_cell_type

Ribonucleotide reductase small subunits

Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 1174–1185

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mutagenesis, EPR and catalytic assays · source_derived_draft · unverified_draft

### iron-rrm2-iron-radical Human RRM2 radical-center tyrosine mutations abolished the detectable stable radical and ribonucleotide-reductase activity in the tested assays. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: DNA building-block synthesis needs a functioning iron/radical enzyme system. organism: Human RRM2 and RRM2B proteins tissue_or_cell_type: Ribonucleotide reductase small subunits experimental_model: Mutagenesis, EPR and catalytic assays limitations: Purified enzyme mechanisms; no recommendation to increase dietary iron for DNA synthesis. exposure: Conserved tyrosine mutations around the diiron center evidence_span: {"source_cache": "artifacts/iron-research/16373698.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0d3e9b3d6c8961f94af38195eab5b0b3180c321da1c7ca75ae956036a60b16cc", "start_char": 0, "end_char": 1165, "text_sha256": "0d3e9b3d6c8961f94af38195eab5b0b3180c321da1c7ca75ae956036a60b16cc"} [iron-p16373698] A dityrosyl-diiron radical cofactor center is essential for human ribonucleotide reductases. (2005). https://pubmed.ncbi.nlm.nih.gov/16373698/ DOI: 10.1158/1535-7163.mct-05-0273

evidence_span

{"source_cache": "artifacts/iron-research/16373698.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0d3e9b3d6c8961f94af38195eab5b0b3180c321da1c7ca75ae956036a60b16cc", "start_char": 0, "end_char": 1165, "text_sha256": "0d3e9b3d6c8961f94af38195eab5b0b3180c321da1c7ca75ae956036a60b16cc"}

experimental_model

Mutagenesis, EPR and catalytic assays

exposure

Conserved tyrosine mutations around the diiron center

limitations

Purified enzyme mechanisms; no recommendation to increase dietary iron for DNA synthesis.

nutrient_topic

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

organism

Human RRM2 and RRM2B proteins

plain_language

The related small subunit is recorded separately so its role is not lost inside a generic enzyme label.

primary_references

[iron-p16373698] A dityrosyl-diiron radical cofactor center is essential for human ribonucleotide reductases. (2005). https://pubmed.ncbi.nlm.nih.gov/16373698/ DOI: 10.1158/1535-7163.mct-05-0273

tissue_or_cell_type

Ribonucleotide reductase small subunits

Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 1187–1198

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mutagenesis, EPR and catalytic assays · source_derived_draft · unverified_draft

### iron-rrm2b-iron-radical The corresponding conserved-tyrosine perturbation also disabled the radical and catalytic activity of the human p53R2/RRM2B system. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: The related small subunit is recorded separately so its role is not lost inside a generic enzyme label. organism: Human RRM2 and RRM2B proteins tissue_or_cell_type: Ribonucleotide reductase small subunits experimental_model: Mutagenesis, EPR and catalytic assays limitations: Purified enzyme mechanisms; no recommendation to increase dietary iron for DNA synthesis. exposure: Conserved tyrosine mutations around the diiron center evidence_span: {"source_cache": "artifacts/iron-research/16373698.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0d3e9b3d6c8961f94af38195eab5b0b3180c321da1c7ca75ae956036a60b16cc", "start_char": 0, "end_char": 1165, "text_sha256": "0d3e9b3d6c8961f94af38195eab5b0b3180c321da1c7ca75ae956036a60b16cc"} [iron-p16373698] A dityrosyl-diiron radical cofactor center is essential for human ribonucleotide reductases. (2005). https://pubmed.ncbi.nlm.nih.gov/16373698/ DOI: 10.1158/1535-7163.mct-05-0273

evidence_span

{"source_cache": "artifacts/inositol-research/18364358.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9992644d489f26782d7ef0a70dc13ec5ca48e2b660a011173fba8e0d4e43ae19", "start_char": 0, "end_char": 1004, "text_sha256": "9992644d489f26782d7ef0a70dc13ec5ca48e2b660a011173fba8e0d4e43ae19"}

experimental_model

Human enzyme crystallography and catalytic analysis

exposure

Diiron center and inhibitor-bound structure

limitations

Catabolism of inositol is not evidence that humans synthesize vitamin C from it; the crystal ligand was an inhibitor.

nutrient_topic

Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)

organism

Homo sapiens

plain_language

Two iron atoms are part of this breakdown enzyme, linking inositol metabolism to iron chemistry.

primary_references

[ino-p18364358] Structural and biophysical characterization of human myo-inositol oxygenase. (2008). https://pubmed.ncbi.nlm.nih.gov/18364358/ DOI: 10.1074/jbc.m800348200

tissue_or_cell_type

Purified MIOX

Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 470–481

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

### ino-miox-iron Human MIOX contains a diiron catalytic center involved in oxygen-dependent inositol cleavage. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: Two iron atoms are part of this breakdown enzyme, linking inositol metabolism to iron chemistry. organism: Homo sapiens tissue_or_cell_type: Purified MIOX experimental_model: Human enzyme crystallography and catalytic analysis limitations: Catabolism of inositol is not evidence that humans synthesize vitamin C from it; the crystal ligand was an inhibitor. exposure: Diiron center and inhibitor-bound structure evidence_span: {"source_cache": "artifacts/inositol-research/18364358.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9992644d489f26782d7ef0a70dc13ec5ca48e2b660a011173fba8e0d4e43ae19", "start_char": 0, "end_char": 1004, "text_sha256": "9992644d489f26782d7ef0a70dc13ec5ca48e2b660a011173fba8e0d4e43ae19"} [ino-p18364358] Structural and biophysical characterization of human myo-inositol oxygenase. (2008). https://pubmed.ncbi.nlm.nih.gov/18364358/ DOI: 10.1074/jbc.m800348200

experimental_model

Randomized double-blind three-period crossover; eight days per period; stable iron isotopes.

limitations

The reassuring paper title does not negate its significant high-dose result. Low-dose impact in healthy iron-replete people was an author extrapolation, not the studied population.

nutrient_topic

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

plain_language

EGCG reduced iron absorption at the higher tested dose.

primary_references

Epigallocatechin gallate (EGCG) (TEAVIGO) does not impair nonhaem-iron absorption in man. · 2005 · https://pubmed.ncbi.nlm.nih.gov/16008116/ · DOI 10.1016/j.phymed.2004.07.001

EGCG: receptor signaling, metabolism, nutrient interactions and discovery questions (2026-09-18) · lines 188–194

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Randomized double-blind three-period crossover; eight days per period; stable iron isotopes. · source_derived_draft · unverified_draft

## egcg-iron EGCG reduced iron absorption at the higher tested dose. In 30 women with low iron stores, 150 and 300 mg EGCG reduced relative nonheme-iron absorption by 14% and 27%; the 300 mg comparison with placebo was significant. Model: Randomized double-blind three-period crossover; eight days per period; stable iron isotopes. Limitations: The reassuring paper title does not negate its significant high-dose result. Low-dose impact in healthy iron-replete people was an author extrapolation, not the studied population. Evidence access: primary abstract. Epigallocatechin gallate (EGCG) (TEAVIGO) does not impair nonhaem-iron absorption in man. · 2005 · https://pubmed.ncbi.nlm.nih.gov/16008116/ · DOI 10.1016/j.phymed.2004.07.001