Component

Ferric ammonium citrate

Ferric citrate/ammonium preparation used to supplement extracellular iron; not equivalent to physiological transferrin-bound iron.

6 recorded relationships. Experimental role, claim status and evidence remain attached to each record.

Read recorded mechanisms Open recursive mind map

How nutrients influence it

Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.

How nutrients reach it in more than one step

Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.

Tracing routes…

What it does

Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.

Recorded relationships

What it acts on

  1. Supplementing RPMI/FCS with as little as 5 µM iron as FAC prevented the marked viability loss caused by 5–10 mM ascorbate in LNCaP and PC-3 cultures; protection also occurred at higher tested iron additions.

    Ferric ammonium citrate → Prostate cancer-cell viability source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    true
    evidence_location
    Figure 1a–b; treatment Methods
    experimental_model
    Human LNCaP and PC-3 monolayers in RPMI-1640 +10% FCS; MTT and crystal-violet viability assays
    exposure
    5 or 10 mM freshly neutralized ascorbic acid, 2 h, then wash/recovery; FAC adds 5–30 µM iron to medium containing 5.6 ±1.3 µM total iron.
    limitations
    FAC supplementation changes iron speciation as well as concentration; matching plasma total iron does not reconstruct transferrin binding or tissue interstitial chemistry. No clinical efficacy conclusion.
    nutrient_topic
    Vitamin C research collection; topical membership is not evidence of a direct dietary effect. · Vitamin C
    organism
    Homo sapiens
    plain_language
    In this medium, extra iron protected the prostate cancer cells from high-concentration vitamin C.
    primary_references
    [c-reg-mojic] Extracellular iron diminishes anticancer effects of vitamin C: an in vitro study. (2014). https://pubmed.ncbi.nlm.nih.gov/25092529/ DOI: 10.1038/srep05955
    tissue_or_cell_type
    Prostate carcinoma cells

    Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1285–1297

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human LNCaP and PC-3 monolayers in RPMI-1640 +10% FCS; MTT and crystal-violet viability assays · source_derived_draft · unverified_draft

    ### c-reg-extracellular-iron-cytoprotection Supplementing RPMI/FCS with as little as 5 µM iron as FAC prevented the marked viability loss caused by 5–10 mM ascorbate in LNCaP and PC-3 cultures; protection also occurred at higher tested iron additions. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: In this medium, extra iron protected the prostate cancer cells from high-concentration vitamin C. organism: Homo sapiens tissue_or_cell_type: Prostate carcinoma cells experimental_model: Human LNCaP and PC-3 monolayers in RPMI-1640 +10% FCS; MTT and crystal-violet viability assays limitations: FAC supplementation changes iron speciation as well as concentration; matching plasma total iron does not reconstruct transferrin binding or tissue interstitial chemistry. No clinical efficacy conclusion. exposure: 5 or 10 mM freshly neutralized ascorbic acid, 2 h, then wash/recovery; FAC adds 5–30 µM iron to medium containing 5.6 ±1.3 µM total iron. cross_nutrient: true evidence_location: Figure 1a–b; treatment Methods [c-reg-mojic] Extracellular iron diminishes anticancer effects of vitamin C: an in vitro study. (2014). https://pubmed.ncbi.nlm.nih.gov/25092529/ DOI: 10.1038/srep05955
    Complete structured claim and evidence

  2. In RPMI/FCS exposed to 5 mM ascorbate, added 5 µM FAC iron accelerated oxygen consumption/ascorbate oxidation but reduced detectable peroxide accumulation, showing that faster oxidation need not yield a larger steady peroxide pool.

    Ferric ammonium citrate → Extracellular hydrogen peroxide accumulation source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    true
    evidence_location
    Figure 2a–b; Oximetry Methods
    experimental_model
    Cell-free medium oximetry; peroxide inferred from catalase-triggered oxygen release
    exposure
    5 mM ascorbate ±5 µM FAC iron; oxygen trace and 600 U catalase addition after about 15 min.
    limitations
    FAC supplementation changes iron speciation as well as concentration; matching plasma total iron does not reconstruct transferrin binding or tissue interstitial chemistry. No clinical efficacy conclusion. The endpoint measures net peroxide and does not separately determine every elementary redox rate.
    nutrient_topic
    Vitamin C research collection; topical membership is not evidence of a direct dietary effect. · Vitamin C
    organism
    Cell-free bovine-serum-containing medium
    plain_language
    Iron sped up vitamin C oxidation while also helping remove the peroxide produced.
    primary_references
    [c-reg-mojic] Extracellular iron diminishes anticancer effects of vitamin C: an in vitro study. (2014). https://pubmed.ncbi.nlm.nih.gov/25092529/ DOI: 10.1038/srep05955
    tissue_or_cell_type
    RPMI-1640 +10% FCS

    Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1299–1311

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell-free medium oximetry; peroxide inferred from catalase-triggered oxygen release · source_derived_draft · unverified_draft

    ### c-reg-extracellular-iron-peroxide-removal In RPMI/FCS exposed to 5 mM ascorbate, added 5 µM FAC iron accelerated oxygen consumption/ascorbate oxidation but reduced detectable peroxide accumulation, showing that faster oxidation need not yield a larger steady peroxide pool. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Iron sped up vitamin C oxidation while also helping remove the peroxide produced. organism: Cell-free bovine-serum-containing medium tissue_or_cell_type: RPMI-1640 +10% FCS experimental_model: Cell-free medium oximetry; peroxide inferred from catalase-triggered oxygen release limitations: FAC supplementation changes iron speciation as well as concentration; matching plasma total iron does not reconstruct transferrin binding or tissue interstitial chemistry. No clinical efficacy conclusion. The endpoint measures net peroxide and does not separately determine every elementary redox rate. exposure: 5 mM ascorbate ±5 µM FAC iron; oxygen trace and 600 U catalase addition after about 15 min. cross_nutrient: true evidence_location: Figure 2a–b; Oximetry Methods [c-reg-mojic] Extracellular iron diminishes anticancer effects of vitamin C: an in vitro study. (2014). https://pubmed.ncbi.nlm.nih.gov/25092529/ DOI: 10.1038/srep05955
    Complete structured claim and evidence

  3. Adding iron to pharmacological ascorbate increased measured extracellular protein oxidation about threefold in the RPMI/FCS experiment while preserving intracellular thiols. The authors interpreted this as extracellular interception of Fenton-derived oxidants; direct hydroxyl-radical spin trapping was unsuccessful because ascorbate reduced the spin adducts.

    Ferric ammonium citrate → Extracellular protein oxidation source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    true
    evidence_location
    Figure 3a–c; Results discussing failed EPR spin trapping
    experimental_model
    Biochemical extracellular protein-oxidation assay and intracellular thiol-sensitive RSSR EPR assay
    exposure
    5 mM ascorbate ±5 µM FAC iron for 2 h in RPMI-1640 +10% FCS; additional 30 µM iron experiment gave similar results. Thiols assayed using 100 µM RSSR probe.
    limitations
    Observed protein oxidation supports but does not directly prove the proposed hydroxyl-radical buffering mechanism. FAC speciation and medium composition limit tissue extrapolation.
    nutrient_topic
    Vitamin C research collection; topical membership is not evidence of a direct dietary effect. · Vitamin C
    organism
    Homo sapiens LNCaP/PC-3 cells; bovine-serum-containing extracellular medium
    plain_language
    Extra iron shifted more oxidation onto proteins in the culture liquid while protecting the cells. The proposed short-lived radical intermediate could not be directly measured.
    primary_references
    [c-reg-mojic] Extracellular iron diminishes anticancer effects of vitamin C: an in vitro study. (2014). https://pubmed.ncbi.nlm.nih.gov/25092529/ DOI: 10.1038/srep05955
    tissue_or_cell_type
    Prostate cancer-cell cultures and their extracellular RPMI/FCS medium

    Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1313–1325

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Biochemical extracellular protein-oxidation assay and intracellular thiol-sensitive RSSR EPR assay · source_derived_draft · unverified_draft

    ### c-reg-extracellular-protein-oxidation Adding iron to pharmacological ascorbate increased measured extracellular protein oxidation about threefold in the RPMI/FCS experiment while preserving intracellular thiols. The authors interpreted this as extracellular interception of Fenton-derived oxidants; direct hydroxyl-radical spin trapping was unsuccessful because ascorbate reduced the spin adducts. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Extra iron shifted more oxidation onto proteins in the culture liquid while protecting the cells. The proposed short-lived radical intermediate could not be directly measured. organism: Homo sapiens LNCaP/PC-3 cells; bovine-serum-containing extracellular medium tissue_or_cell_type: Prostate cancer-cell cultures and their extracellular RPMI/FCS medium experimental_model: Biochemical extracellular protein-oxidation assay and intracellular thiol-sensitive RSSR EPR assay limitations: Observed protein oxidation supports but does not directly prove the proposed hydroxyl-radical buffering mechanism. FAC speciation and medium composition limit tissue extrapolation. exposure: 5 mM ascorbate ±5 µM FAC iron for 2 h in RPMI-1640 +10% FCS; additional 30 µM iron experiment gave similar results. Thiols assayed using 100 µM RSSR probe. cross_nutrient: true evidence_location: Figure 3a–c; Results discussing failed EPR spin trapping [c-reg-mojic] Extracellular iron diminishes anticancer effects of vitamin C: an in vitro study. (2014). https://pubmed.ncbi.nlm.nih.gov/25092529/ DOI: 10.1038/srep05955
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. Chromium picolinate plus ferric ammonium citrate produced greater insulin-stimulated glucose uptake than ferric ammonium citrate alone in C2C12 cells.

    Chromium(III) picolinate / CrPic → Insulin-stimulated glucose uptake source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/chromium-research/37156991.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e5b7952975edd461bc01f9a4389588789a7d1b7dedf56fb97270051092ae6cda", "start_char": 0, "end_char": 1621, "text_sha256": "e5b7952975edd461bc01f9a4389588789a7d1b7dedf56fb97270051092ae6cda"}
    experimental_model
    C2C12 cell experiments with supporting database pathway analysis
    exposure
    Chromium picolinate, ferric ammonium citrate and combination
    limitations
    Pathway databases generate hypotheses. Co-changing ROS and signaling measurements do not alone establish a unique causal sequence; no human iron-overload treatment was tested.
    nutrient_topic
    Chromium research collection; topical membership is not evidence of a direct dietary effect. · Chromium
    organism
    Mouse C2C12 skeletal-muscle cells
    plain_language
    The chromium compound partly countered an iron-induced glucose-uptake defect in cultured cells.
    primary_references
    [chromium-p37156991] Antagonizing Effects of Chromium Against Iron-Decreased Glucose Uptake by Regulating ROS-Mediated PI3K/Akt/GLUT4 Signaling Pathway in C2C12. (2024). https://pubmed.ncbi.nlm.nih.gov/37156991/ DOI: 10.1007/s12011-023-03695-z
    tissue_or_cell_type
    Cellular glucose uptake, ROS assays and signaling proteins

    Chromium: transport, insulin signaling, nutrient interactions and essentiality debate (2026-09-17) · lines 770–781

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · C2C12 cell experiments with supporting database pathway analysis · source_derived_draft · unverified_draft

    ### chromium-iron-cell-glucose Chromium picolinate plus ferric ammonium citrate produced greater insulin-stimulated glucose uptake than ferric ammonium citrate alone in C2C12 cells. Condition category: normal nutrient_topic: Chromium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The chromium compound partly countered an iron-induced glucose-uptake defect in cultured cells. organism: Mouse C2C12 skeletal-muscle cells tissue_or_cell_type: Cellular glucose uptake, ROS assays and signaling proteins experimental_model: C2C12 cell experiments with supporting database pathway analysis limitations: Pathway databases generate hypotheses. Co-changing ROS and signaling measurements do not alone establish a unique causal sequence; no human iron-overload treatment was tested. exposure: Chromium picolinate, ferric ammonium citrate and combination evidence_span: {"source_cache": "artifacts/chromium-research/37156991.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e5b7952975edd461bc01f9a4389588789a7d1b7dedf56fb97270051092ae6cda", "start_char": 0, "end_char": 1621, "text_sha256": "e5b7952975edd461bc01f9a4389588789a7d1b7dedf56fb97270051092ae6cda"} [chromium-p37156991] Antagonizing Effects of Chromium Against Iron-Decreased Glucose Uptake by Regulating ROS-Mediated PI3K/Akt/GLUT4 Signaling Pathway in C2C12. (2024). https://pubmed.ncbi.nlm.nih.gov/37156991/ DOI: 10.1007/s12011-023-03695-z
    Complete structured claim and evidence

  2. Chromium co-treatment increased GLUT4 levels relative to the iron-only condition, alongside higher PI3K and Akt phosphorylation ratios.

    Chromium(III) picolinate / CrPic → Mouse glucose transporter 4 / Slc2a4 source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/chromium-research/37156991.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e5b7952975edd461bc01f9a4389588789a7d1b7dedf56fb97270051092ae6cda", "start_char": 0, "end_char": 1621, "text_sha256": "e5b7952975edd461bc01f9a4389588789a7d1b7dedf56fb97270051092ae6cda"}
    experimental_model
    C2C12 cell experiments with supporting database pathway analysis
    exposure
    Chromium picolinate, ferric ammonium citrate and combination
    limitations
    Pathway databases generate hypotheses. Co-changing ROS and signaling measurements do not alone establish a unique causal sequence; no human iron-overload treatment was tested.
    nutrient_topic
    Chromium research collection; topical membership is not evidence of a direct dietary effect. · Chromium
    organism
    Mouse C2C12 skeletal-muscle cells
    plain_language
    The glucose transporter and measured signaling steps were less suppressed.
    primary_references
    [chromium-p37156991] Antagonizing Effects of Chromium Against Iron-Decreased Glucose Uptake by Regulating ROS-Mediated PI3K/Akt/GLUT4 Signaling Pathway in C2C12. (2024). https://pubmed.ncbi.nlm.nih.gov/37156991/ DOI: 10.1007/s12011-023-03695-z
    tissue_or_cell_type
    Cellular glucose uptake, ROS assays and signaling proteins

    Chromium: transport, insulin signaling, nutrient interactions and essentiality debate (2026-09-17) · lines 796–807

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · C2C12 cell experiments with supporting database pathway analysis · source_derived_draft · unverified_draft

    ### chromium-iron-cell-glut4 Chromium co-treatment increased GLUT4 levels relative to the iron-only condition, alongside higher PI3K and Akt phosphorylation ratios. Condition category: normal nutrient_topic: Chromium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The glucose transporter and measured signaling steps were less suppressed. organism: Mouse C2C12 skeletal-muscle cells tissue_or_cell_type: Cellular glucose uptake, ROS assays and signaling proteins experimental_model: C2C12 cell experiments with supporting database pathway analysis limitations: Pathway databases generate hypotheses. Co-changing ROS and signaling measurements do not alone establish a unique causal sequence; no human iron-overload treatment was tested. exposure: Chromium picolinate, ferric ammonium citrate and combination evidence_span: {"source_cache": "artifacts/chromium-research/37156991.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e5b7952975edd461bc01f9a4389588789a7d1b7dedf56fb97270051092ae6cda", "start_char": 0, "end_char": 1621, "text_sha256": "e5b7952975edd461bc01f9a4389588789a7d1b7dedf56fb97270051092ae6cda"} [chromium-p37156991] Antagonizing Effects of Chromium Against Iron-Decreased Glucose Uptake by Regulating ROS-Mediated PI3K/Akt/GLUT4 Signaling Pathway in C2C12. (2024). https://pubmed.ncbi.nlm.nih.gov/37156991/ DOI: 10.1007/s12011-023-03695-z
    Complete structured claim and evidence

  3. The combination had a lower intracellular ROS assay signal than ferric ammonium citrate alone.

    Chromium(III) picolinate / CrPic → Cellular ROS assay signal source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/chromium-research/37156991.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e5b7952975edd461bc01f9a4389588789a7d1b7dedf56fb97270051092ae6cda", "start_char": 0, "end_char": 1621, "text_sha256": "e5b7952975edd461bc01f9a4389588789a7d1b7dedf56fb97270051092ae6cda"}
    experimental_model
    C2C12 cell experiments with supporting database pathway analysis
    exposure
    Chromium picolinate, ferric ammonium citrate and combination
    limitations
    Pathway databases generate hypotheses. Co-changing ROS and signaling measurements do not alone establish a unique causal sequence; no human iron-overload treatment was tested.
    nutrient_topic
    Chromium research collection; topical membership is not evidence of a direct dietary effect. · Chromium
    organism
    Mouse C2C12 skeletal-muscle cells
    plain_language
    A measured oxidative-stress signal was lower with co-treatment.
    primary_references
    [chromium-p37156991] Antagonizing Effects of Chromium Against Iron-Decreased Glucose Uptake by Regulating ROS-Mediated PI3K/Akt/GLUT4 Signaling Pathway in C2C12. (2024). https://pubmed.ncbi.nlm.nih.gov/37156991/ DOI: 10.1007/s12011-023-03695-z
    tissue_or_cell_type
    Cellular glucose uptake, ROS assays and signaling proteins

    Chromium: transport, insulin signaling, nutrient interactions and essentiality debate (2026-09-17) · lines 783–794

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · C2C12 cell experiments with supporting database pathway analysis · source_derived_draft · unverified_draft

    ### chromium-iron-cell-ros The combination had a lower intracellular ROS assay signal than ferric ammonium citrate alone. Condition category: normal nutrient_topic: Chromium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A measured oxidative-stress signal was lower with co-treatment. organism: Mouse C2C12 skeletal-muscle cells tissue_or_cell_type: Cellular glucose uptake, ROS assays and signaling proteins experimental_model: C2C12 cell experiments with supporting database pathway analysis limitations: Pathway databases generate hypotheses. Co-changing ROS and signaling measurements do not alone establish a unique causal sequence; no human iron-overload treatment was tested. exposure: Chromium picolinate, ferric ammonium citrate and combination evidence_span: {"source_cache": "artifacts/chromium-research/37156991.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e5b7952975edd461bc01f9a4389588789a7d1b7dedf56fb97270051092ae6cda", "start_char": 0, "end_char": 1621, "text_sha256": "e5b7952975edd461bc01f9a4389588789a7d1b7dedf56fb97270051092ae6cda"} [chromium-p37156991] Antagonizing Effects of Chromium Against Iron-Decreased Glucose Uptake by Regulating ROS-Mediated PI3K/Akt/GLUT4 Signaling Pathway in C2C12. (2024). https://pubmed.ncbi.nlm.nih.gov/37156991/ DOI: 10.1007/s12011-023-03695-z
    Complete structured claim and evidence

In the sources

Preserved passages that mention this component, quoted exactly. Open one to read it in context.

    This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.

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