Component

Nitrate ion

NO3−; competing anion in human NIS assays.

5 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. Nitrate inhibited radioactive iodide uptake in CHO cells stably expressing human NIS.

    Nitrate ion → Cellular iodide uptake source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    false
    experimental_model
    CHO cells stably expressing human NIS; individual and mixed anion exposures with 125I uptake
    exposure
    Concentration-response experiments with individual anions and 125I uptake; exact concentration series not reported in abstract.
    limitations
    In vitro potency is not a human dietary exposure threshold, whole-body iodine displacement claim or supplementation instruction.
    nutrient_topic
    Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
    organism
    Human NIS in hamster CHO cells
    plain_language
    A competing anion reduced iodide entry through human NIS in a cell assay.
    primary_references
    [iodine-trans-inhibitors2004] Relative potencies and additivity of perchlorate, thiocyanate, nitrate, and iodide on the inhibition of radioactive iodide uptake by the human sodium iodide symporter. (2004). https://pubmed.ncbi.nlm.nih.gov/15650353/ DOI: 10.1089/thy.2004.14.1012
    tissue_or_cell_type
    Cell plasma membrane

    Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 427–438

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · CHO cells stably expressing human NIS; individual and mixed anion exposures with 125I uptake · source_derived_draft · unverified_draft

    ### iodine-trans-nitrate-inhibits Nitrate inhibited radioactive iodide uptake in CHO cells stably expressing human NIS. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A competing anion reduced iodide entry through human NIS in a cell assay. organism: Human NIS in hamster CHO cells tissue_or_cell_type: Cell plasma membrane experimental_model: CHO cells stably expressing human NIS; individual and mixed anion exposures with 125I uptake limitations: In vitro potency is not a human dietary exposure threshold, whole-body iodine displacement claim or supplementation instruction. exposure: Concentration-response experiments with individual anions and 125I uptake; exact concentration series not reported in abstract. cross_nutrient: false [iodine-trans-inhibitors2004] Relative potencies and additivity of perchlorate, thiocyanate, nitrate, and iodide on the inhibition of radioactive iodide uptake by the human sodium iodide symporter. (2004). https://pubmed.ncbi.nlm.nih.gov/15650353/ DOI: 10.1089/thy.2004.14.1012
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. Sildenafil alone can cause mean peak reductions in systolic and diastolic blood pressure of 10 and 7 millimetres of mercury that are not dose related while heart rate is unchanged, and sildenafil and nitrates both increase cyclic GMP levels in the systemic circulation but at different points along the nitric oxide to cyclic GMP pathway, so the combination is contraindicated because they synergistically potentiate vasodilation; retrospective analysis of concomitant antihypertensive medications did not indicate an increase in adverse events, and concurrent renal or hepatic impairment or CYP3A4 inhibitors could increase systemic exposure.

    Sildenafil → Cyclic guanosine monophosphate source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    biomarker_context Imported condition classification; unverified.
    evidence_span
    {"source_cache": "artifacts/sildenafil-research/10078541.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e65228d2afaad9ce38dccf42c7279ec6b562746aa27b121bf5e5782f36cbe593", "start_char": 0, "end_char": 2772, "text_sha256": "e65228d2afaad9ce38dccf42c7279ec6b562746aa27b121bf5e5782f36cbe593"}
    experimental_model
    Review of the cardiovascular profile from the clinical development programme and post-marketing surveillance
    exposure
    Sildenafil alone and with antihypertensive classes, across clinical trials and spontaneous reports
    limitations
    A manufacturer-authored review of the development programme rather than an independent analysis, and the post-marketing comparisons are retrospective.
    nutrient_topic
    Sildenafil research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from its N-desmethyl metabolite and its target enzyme from the homologous retinal PDE6. · Sildenafil
    organism
    Human
    plain_language
    Both act on the same pathway at different points, which is why together they multiply rather than add.
    primary_references
    [sil-p10078541] Overall cardiovascular profile of sildenafil citrate. (1999). https://pubmed.ncbi.nlm.nih.gov/10078541/ DOI: 10.1016/s0002-9149(99)00046-6
    tissue_or_cell_type
    Cardiovascular system
    trigger_kind
    biomarker_context Imported condition classification; unverified.

    Sildenafil: the enzyme it occupies instead of the substrate, why it cannot start a signal it can only preserve, the organic nitrate interaction that follows from that, the homologous retinal enzyme ten-fold away, and the pulmonary circulation where the same mechanism became a second indication (2026-09-22) · lines 431–442

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Review of the cardiovascular profile from the clinical development programme and post-marketing surveillance · source_derived_draft · unverified_draft

    ### sil-two-points-on-one-pathway Sildenafil alone can cause mean peak reductions in systolic and diastolic blood pressure of 10 and 7 millimetres of mercury that are not dose related while heart rate is unchanged, and sildenafil and nitrates both increase cyclic GMP levels in the systemic circulation but at different points along the nitric oxide to cyclic GMP pathway, so the combination is contraindicated because they synergistically potentiate vasodilation; retrospective analysis of concomitant antihypertensive medications did not indicate an increase in adverse events, and concurrent renal or hepatic impairment or CYP3A4 inhibitors could increase systemic exposure. Condition category: biomarker_context nutrient_topic: Sildenafil research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from its N-desmethyl metabolite and its target enzyme from the homologous retinal PDE6. plain_language: Both act on the same pathway at different points, which is why together they multiply rather than add. organism: Human tissue_or_cell_type: Cardiovascular system experimental_model: Review of the cardiovascular profile from the clinical development programme and post-marketing surveillance limitations: A manufacturer-authored review of the development programme rather than an independent analysis, and the post-marketing comparisons are retrospective. exposure: Sildenafil alone and with antihypertensive classes, across clinical trials and spontaneous reports evidence_span: {"source_cache": "artifacts/sildenafil-research/10078541.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e65228d2afaad9ce38dccf42c7279ec6b562746aa27b121bf5e5782f36cbe593", "start_char": 0, "end_char": 2772, "text_sha256": "e65228d2afaad9ce38dccf42c7279ec6b562746aa27b121bf5e5782f36cbe593"} [sil-p10078541] Overall cardiovascular profile of sildenafil citrate. (1999). https://pubmed.ncbi.nlm.nih.gov/10078541/ DOI: 10.1016/s0002-9149(99)00046-6
    Complete structured claim and evidence

  2. Mixtures of perchlorate, thiocyanate and nitrate inhibited human NIS-mediated iodide uptake consistently with an additive common competitive model, without evidence of synergism.

    Perchlorate ion → Cellular iodide uptake source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    false
    experimental_model
    CHO cells stably expressing human NIS; individual and mixed anion exposures with 125I uptake
    exposure
    Joint Hill-equation fit; perchlorate molar potency was 15 times thiocyanate and 240 times nitrate.
    limitations
    Relative potencies and lack of synergy are assay-specific; they do not predict individual human thyroid outcomes from environmental concentrations.
    nutrient_topic
    Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
    organism
    Human NIS in hamster CHO cells
    plain_language
    These competitors combined approximately additively in the tested cell system.
    primary_references
    [iodine-trans-inhibitors2004] Relative potencies and additivity of perchlorate, thiocyanate, nitrate, and iodide on the inhibition of radioactive iodide uptake by the human sodium iodide symporter. (2004). https://pubmed.ncbi.nlm.nih.gov/15650353/ DOI: 10.1089/thy.2004.14.1012
    tissue_or_cell_type
    Cell plasma membrane

    Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 440–451

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · CHO cells stably expressing human NIS; individual and mixed anion exposures with 125I uptake · source_derived_draft · unverified_draft

    ### iodine-trans-inhibitor-additivity Mixtures of perchlorate, thiocyanate and nitrate inhibited human NIS-mediated iodide uptake consistently with an additive common competitive model, without evidence of synergism. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: These competitors combined approximately additively in the tested cell system. organism: Human NIS in hamster CHO cells tissue_or_cell_type: Cell plasma membrane experimental_model: CHO cells stably expressing human NIS; individual and mixed anion exposures with 125I uptake limitations: Relative potencies and lack of synergy are assay-specific; they do not predict individual human thyroid outcomes from environmental concentrations. exposure: Joint Hill-equation fit; perchlorate molar potency was 15 times thiocyanate and 240 times nitrate. cross_nutrient: false [iodine-trans-inhibitors2004] Relative potencies and additivity of perchlorate, thiocyanate, nitrate, and iodide on the inhibition of radioactive iodide uptake by the human sodium iodide symporter. (2004). https://pubmed.ncbi.nlm.nih.gov/15650353/ DOI: 10.1089/thy.2004.14.1012
    Complete structured claim and evidence

  3. Plasma NOx remained elevated for 8 h after beetroot juice and 5 h after whole beetroot despite undetectable plasma betanin.

    Beetroot juice and whole beetroot in the 2017 pharmacokinetic study → Plasma NOx in the beetroot pharmacokinetic study source_derived_draftungraded
    Experimental context and source evidence
    dose
    250 mL beetroot juice or 300 g whole beetroot versus placebo
    duration
    Baseline and 1, 2, 3, 5 and 8 h
    evidence_access
    Primary PubMed abstract; detailed exposure for PMID 23931157 additionally checked in publisher results. No uninspected full text is claimed.
    evidence_scope
    literature_reviewed; source-derived curation, not universally established human effects
    experimental_model
    Ten healthy men in a randomized crossover study
    limitations
    An undetectable parent compound is not proof of zero absorption. Food matrix, degradation and analytical methods differ from the cactus pear study. NOx is not itself a measurement of a betanin mechanism. Mixed-food nitrate-related observation; not a claim that betalains generate NO or mediate nitrate-associated performance effects.
    nutrient_topic
    Betalains collection; each molecular form, species, exposure and preparation remains explicit. · Betalains
    organism
    Ten healthy men in a randomized crossover study
    plain_language
    Plasma NOx remained elevated for 8 h after beetroot juice and 5 h after whole beetroot despite undetectable plasma betanin.
    primary_references
    The plasma bioavailability of nitrate and betanin from Beta vulgaris rubra in humans. (2017). https://pubmed.ncbi.nlm.nih.gov/26873098/ DOI: 10.1007/s00394-016-1173-5
    route
    Oral food/drink
    tissue
    Venous plasma

    Betalains: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 537–545

    Original AI-assisted curation of twelve primary research papers; study-specific PubMed/DOI links and limitations retained. Not publisher full text. · supports · Ten healthy men in a randomized crossover study · source_derived_draft · unverified_draft

    ## betalains-beetroot-nox-separate Plasma NOx remained elevated for 8 h after beetroot juice and 5 h after whole beetroot despite undetectable plasma betanin. Model/species: Ten healthy men in a randomized crossover study Tissue: Venous plasma Exposure: 250 mL beetroot juice or 300 g whole beetroot versus placebo Route: Oral food/drink Duration: Baseline and 1, 2, 3, 5 and 8 h Limits: An undetectable parent compound is not proof of zero absorption. Food matrix, degradation and analytical methods differ from the cactus pear study. NOx is not itself a measurement of a betanin mechanism. Mixed-food nitrate-related observation; not a claim that betalains generate NO or mediate nitrate-associated performance effects. Primary reference: The plasma bioavailability of nitrate and betanin from Beta vulgaris rubra in humans. (2017). https://pubmed.ncbi.nlm.nih.gov/26873098/ DOI: 10.1007/s00394-016-1173-5
    Complete structured claim and evidence

  4. An uncontrolled 12-person nitrate/garlic combination study reported lower systolic pressure after two weeks, persisting at four weeks.

    Vascanox HP nitrate/garlic combination studied in 2023 → Blood-pressure readout in the 2023 Vascanox open-label study source_derived_draftungraded
    Experimental context and source evidence
    acting_entity
    vascanox-hp-2023
    dose
    Vascanox HP combination; constituent doses not retrieved
    duration
    Four weeks
    evidence_access
    Primary abstract
    experimental_comparison
    Within-person baseline; no placebo or factorial comparison
    experimental_model
    Twelve participants completing an open-label combination study
    interpretation_status
    Source-derived research curation; not independent primary verification
    limitations
    No placebo or ingredient-factorial arms: cannot establish SAC contribution, nitrate contribution, interaction or synergy.
    nutrient_topic
    S-allylcysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · S-allyl-L-cysteine / SAC
    organism
    Homo sapiens
    plain_language
    A cross-compound human lead remains available without assigning the effect to SAC.
    primary_references
    [37849591] Effects of S-Allylcysteine-Rich Garlic Extract and Dietary Inorganic Nitrate Formula on Blood Pressure and Salivary Nitric Oxide: An Open-Label Clinical Trial Among Hypertensive Subjects. · 2023 · https://pubmed.ncbi.nlm.nih.gov/37849591/ · DOI 10.7759/cureus.45369
    route
    Oral
    tissue_or_cell_type
    Twelve participants completing an open-label combination study

    S-allylcysteine: sulfur signaling, redox responses and cross-nutrient mechanisms (2026-09-20) · lines 455–462

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Twelve participants completing an open-label combination study · source_derived_draft · unverified_draft

    ## s-allylcysteine-nitrate-combination A cross-compound human lead remains available without assigning the effect to SAC. An uncontrolled 12-person nitrate/garlic combination study reported lower systolic pressure after two weeks, persisting at four weeks. Model: Twelve participants completing an open-label combination study Limitations: No placebo or ingredient-factorial arms: cannot establish SAC contribution, nitrate contribution, interaction or synergy. Evidence access: Primary abstract [37849591] Effects of S-Allylcysteine-Rich Garlic Extract and Dietary Inorganic Nitrate Formula on Blood Pressure and Salivary Nitric Oxide: An Open-Label Clinical Trial Among Hypertensive Subjects. · 2023 · https://pubmed.ncbi.nlm.nih.gov/37849591/ · DOI 10.7759/cureus.45369 Structured context: {"organism": "Homo sapiens", "tissue_or_cell_type": "Twelve participants completing an open-label combination study", "dose": "Vascanox HP combination; constituent doses not retrieved", "duration": "Four weeks", "route": "Oral", "experimental_comparison": "Within-person baseline; no placebo or factorial comparison", "acting_entity": "vascanox-hp-2023", "interpretation_status": "Source-derived research curation; not independent primary verification"}
    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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