Nutrient chapter

Iodine

Independent biological entity. Read linked claims for experimental scope and context.

119 recorded mechanisms · 20 availability situations · 5 preserved sources. Draft and verified records are labeled separately.

Read recorded mechanisms Open recursive mind map

The mechanisms

What the sources say this nutrient does, one relationship at a time. Plain wording comes first; the technical statement follows.

DIO1 converts T4 into the active thyroid hormone T3.
DIO1 catalyzes outer-ring deiodination of T4 to T3 in functional enzyme-expression experiments.
DIO1 → T3 source_derived_draftliterature_reviewed:direct_experimental
Experimental context and source evidence
experimental_model
Human liver/kidney cDNA cloning and heterologous enzyme expression.
limitations
This reaction alone cannot diagnose hidden tissue hypothyroidism from normal blood tests or quantify benefit from selenium intake.
organism
Human protein in a heterologous expression system
Selenium: literature corrections and mechanism additions · lines 998–1007
Metabolic Ledger literature curation, 17 September 2026; primary papers linked individually · supports · Human liver/kidney cDNA cloning and heterologous enzyme expression. · secondary_verified · secondary_verified
## dio1-t4-to-t3 DIO1 converts T4 into the active thyroid hormone T3. DIO1 catalyzes outer-ring deiodination of T4 to T3 in functional enzyme-expression experiments. Experimental model: Human liver/kidney cDNA cloning and heterologous enzyme expression. Organism: Human protein in a heterologous expression system Limitations: This reaction alone cannot diagnose hidden tissue hypothyroidism from normal blood tests or quantify benefit from selenium intake. Primary reference: [Cloning and in vitro expression of the human selenoprotein, type I iodothyronine deiodinase](https://pubmed.ncbi.nlm.nih.gov/1400883/)
Complete structured claim and evidence
DIO2 converts T4 into the active thyroid hormone T3.
DIO2 catalyzes outer-ring deiodination of T4 to T3 in functional enzyme-expression experiments.
DIO2 → T3 source_derived_draftliterature_reviewed:direct_experimental
Experimental context and source evidence
experimental_model
Rat and human DIO2 cDNA characterization and functional expression.
limitations
This reaction alone cannot diagnose hidden tissue hypothyroidism from normal blood tests or quantify benefit from selenium intake.
organism
Human and rat
Selenium: literature corrections and mechanism additions · lines 1009–1018
Metabolic Ledger literature curation, 17 September 2026; primary papers linked individually · supports · Rat and human DIO2 cDNA characterization and functional expression. · secondary_verified · secondary_verified
## dio2-t4-to-t3 DIO2 converts T4 into the active thyroid hormone T3. DIO2 catalyzes outer-ring deiodination of T4 to T3 in functional enzyme-expression experiments. Experimental model: Rat and human DIO2 cDNA characterization and functional expression. Organism: Human and rat Limitations: This reaction alone cannot diagnose hidden tissue hypothyroidism from normal blood tests or quantify benefit from selenium intake. Primary reference: [Cloning of the mammalian type II iodothyronine deiodinase](https://www.jci.org/articles/view/118806)
Complete structured claim and evidence
DIO3 lowers thyroid-hormone activity by converting T4 to reverse T3.
DIO3 catalyzes inner-ring deiodination of T4 to reverse T3 in functional placental-enzyme studies.
DIO3 → rT3 source_derived_draftliterature_reviewed:direct_experimental
Experimental context and source evidence
experimental_model
Human placental DIO3 cloning and functional expression.
limitations
This experiment-specific relationship does not establish a human dietary-deficiency threshold or supplementation benefit.
organism
Human placental protein in an expression system
Selenium: literature corrections and mechanism additions · lines 1020–1029
Metabolic Ledger literature curation, 17 September 2026; primary papers linked individually · supports · Human placental DIO3 cloning and functional expression. · secondary_verified · secondary_verified
## dio3-thyroxine-inactivation DIO3 lowers thyroid-hormone activity by converting T4 to reverse T3. DIO3 catalyzes inner-ring deiodination of T4 to reverse T3 in functional placental-enzyme studies. Experimental model: Human placental DIO3 cloning and functional expression. Organism: Human placental protein in an expression system Limitations: This experiment-specific relationship does not establish a human dietary-deficiency threshold or supplementation benefit. Primary reference: [Type 3 iodothyronine deiodinase: cloning, in vitro expression, and functional analysis of the placental selenoenzyme](https://www.jci.org/articles/view/118299)
Complete structured claim and evidence
DIO3 lowers thyroid-hormone activity by converting T3 to 3,3-prime-T2.
DIO3 catalyzes inner-ring deiodination of T3 to 3,3-prime-T2 in functional placental-enzyme studies.
DIO3 → 3,3-prime-T2 source_derived_draftliterature_reviewed:direct_experimental
Experimental context and source evidence
experimental_model
Human placental DIO3 cloning and functional expression.
limitations
This experiment-specific relationship does not establish a human dietary-deficiency threshold or supplementation benefit.
organism
Human placental protein in an expression system
Selenium: literature corrections and mechanism additions · lines 1031–1040
Metabolic Ledger literature curation, 17 September 2026; primary papers linked individually · supports · Human placental DIO3 cloning and functional expression. · secondary_verified · secondary_verified
## dio3-triiodothyronine-inactivation DIO3 lowers thyroid-hormone activity by converting T3 to 3,3-prime-T2. DIO3 catalyzes inner-ring deiodination of T3 to 3,3-prime-T2 in functional placental-enzyme studies. Experimental model: Human placental DIO3 cloning and functional expression. Organism: Human placental protein in an expression system Limitations: This experiment-specific relationship does not establish a human dietary-deficiency threshold or supplementation benefit. Primary reference: [Type 3 iodothyronine deiodinase: cloning, in vitro expression, and functional analysis of the placental selenoenzyme](https://www.jci.org/articles/view/118299)
Complete structured claim and evidence
RXRA complexed with TR beta and enhanced thyroid-response-element binding.
Retinoid X receptor alpha → Thyroid hormone receptor beta source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Vitamin A-iodine: shared receptor machinery for an iodine-containing hormone; not evidence of iodine repletion.
evidence_locator
Figure 3
experimental_model
Recombinant receptors, gel shifts, coimmunoprecipitation and CV-1 reporters.
exposure
Reconstituted TR beta/RXRA
limitations
No iodine nutritional manipulation.
nutrient_topic
Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A
organism
Recombinant receptors
plain_language
A receptor used by retinoids also supports thyroid-hormone DNA recognition.
primary_references
[va-kliewer-1992] Retinoid X receptor interacts with nuclear receptors in retinoic acid, thyroid hormone and vitamin D3 signalling (1992). https://pubmed.ncbi.nlm.nih.gov/1310351/ DOI: 10.1038/355446a0
tissue_or_cell_type
Cell-free DNA-binding assay
Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1109–1121
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant receptors, gel shifts, coimmunoprecipitation and CV-1 reporters. · source_derived_draft · unverified_draft
### va-sig-rxra-thrb-partnership RXRA complexed with TR beta and enhanced thyroid-response-element binding. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: A receptor used by retinoids also supports thyroid-hormone DNA recognition. organism: Recombinant receptors tissue_or_cell_type: Cell-free DNA-binding assay experimental_model: Recombinant receptors, gel shifts, coimmunoprecipitation and CV-1 reporters. limitations: No iodine nutritional manipulation. evidence_locator: Figure 3 cross_nutrient: Vitamin A-iodine: shared receptor machinery for an iodine-containing hormone; not evidence of iodine repletion. exposure: Reconstituted TR beta/RXRA [va-kliewer-1992] Retinoid X receptor interacts with nuclear receptors in retinoic acid, thyroid hormone and vitamin D3 signalling (1992). https://pubmed.ncbi.nlm.nih.gov/1310351/ DOI: 10.1038/355446a0
Complete structured claim and evidence
Vitamin A without iodine supplementation lowered TSH in the iodine-deficient study setting.
All-trans-retinyl palmitate → Serum TSH concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Vitamin A/iodine -> thyroid feedback.
experimental_model
404 children; factorial trial.
limitations
TSH-beta transcriptional suppression is an explanation, not a directly measured step in these children.
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 status affected how strongly the thyroid was being stimulated.
primary_references
[va-zimmermann2007-iodine] Vitamin A supplementation in iodine-deficient African children decreases thyrotropin stimulation of the thyroid and reduces the goiter rate (2007). https://pubmed.ncbi.nlm.nih.gov/17921382/ DOI: 10.1093/ajcn/86.4.1040
tissue_or_cell_type
Pituitary-thyroid axis
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1578–1588
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 404 children; factorial trial. · source_derived_draft · unverified_draft
### va-iodine-context-lowers-tsh Vitamin A without iodine supplementation lowered TSH in the iodine-deficient study setting. Condition category: nutrient_deficiency nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin A status affected how strongly the thyroid was being stimulated. organism: Homo sapiens tissue_or_cell_type: Pituitary-thyroid axis experimental_model: 404 children; factorial trial. limitations: TSH-beta transcriptional suppression is an explanation, not a directly measured step in these children. cross_nutrient: Vitamin A/iodine -> thyroid feedback. [va-zimmermann2007-iodine] Vitamin A supplementation in iodine-deficient African children decreases thyrotropin stimulation of the thyroid and reduces the goiter rate (2007). https://pubmed.ncbi.nlm.nih.gov/17921382/ DOI: 10.1093/ajcn/86.4.1040
Complete structured claim and evidence
Thyroid volume and thyroglobulin decreased with vitamin A alone; total T4 showed no significant treatment-interaction effect.
All-trans-retinyl palmitate → Thyroid volume source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
experimental_model
Same trial.
limitations
Iodine treatment remained effective; nutrient roles are not interchangeable.
nutrient_topic
Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A
organism
Homo sapiens
plain_language
Reduced thyroid enlargement did not establish a universal rise in thyroid hormone.
primary_references
[va-zimmermann2007-iodine] Vitamin A supplementation in iodine-deficient African children decreases thyrotropin stimulation of the thyroid and reduces the goiter rate (2007). https://pubmed.ncbi.nlm.nih.gov/17921382/ DOI: 10.1093/ajcn/86.4.1040
tissue_or_cell_type
Thyroid
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1590–1599
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Same trial. · source_derived_draft · unverified_draft
### va-iodine-context-thyroid-volume Thyroid volume and thyroglobulin decreased with vitamin A alone; total T4 showed no significant treatment-interaction effect. Condition category: nutrient_deficiency nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Reduced thyroid enlargement did not establish a universal rise in thyroid hormone. organism: Homo sapiens tissue_or_cell_type: Thyroid experimental_model: Same trial. limitations: Iodine treatment remained effective; nutrient roles are not interchangeable. [va-zimmermann2007-iodine] Vitamin A supplementation in iodine-deficient African children decreases thyrotropin stimulation of the thyroid and reduces the goiter rate (2007). https://pubmed.ncbi.nlm.nih.gov/17921382/ DOI: 10.1093/ajcn/86.4.1040
Complete structured claim and evidence
Thyroxine adsorbed to calcium carbonate under acidic in-vitro conditions.
Calcium carbonate → T4 source_derived_draftungraded
Experimental context and source evidence
experimental_model
In-vitro adsorption arm accompanying a 20-patient study.
limitations
Supports an absorption-interference mechanism; does not show a systemic blockade of deiodinases.
nutrient_topic
Calcium research collection; topical membership is not evidence of a direct dietary effect. · Calcium
organism
Homo sapiens
plain_language
A calcium preparation can bind a thyroid medicine before absorption.
primary_references
[cal-clin-singh2000] Effect of calcium carbonate on the absorption of levothyroxine (2000). https://pubmed.ncbi.nlm.nih.gov/10838651/ DOI: 10.1001/jama.283.21.2822
tissue_or_cell_type
Cell-free acidic solution
Calcium: mechanism-first literature curation (2026-09-17) · lines 1389–1398
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · In-vitro adsorption arm accompanying a 20-patient study. · source_derived_draft · unverified_draft
### cal-carbonate-thyroxine-adsorption Thyroxine adsorbed to calcium carbonate under acidic in-vitro conditions. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A calcium preparation can bind a thyroid medicine before absorption. organism: Homo sapiens tissue_or_cell_type: Cell-free acidic solution experimental_model: In-vitro adsorption arm accompanying a 20-patient study. limitations: Supports an absorption-interference mechanism; does not show a systemic blockade of deiodinases. [cal-clin-singh2000] Effect of calcium carbonate on the absorption of levothyroxine (2000). https://pubmed.ncbi.nlm.nih.gov/10838651/ DOI: 10.1001/jama.283.21.2822
Complete structured claim and evidence
Simultaneous calcium carbonate reduced measured levothyroxine absorption in a seven-volunteer experiment.
Calcium carbonate → Levothyroxine absorption source_derived_draftungraded
Experimental context and source evidence
experimental_model
Two visits separated by four weeks; serum-based pharmacokinetic estimation.
exposure
1000 micrograms levothyroxine with or without 2 g elemental calcium as carbonate; six-hour total absorption differed (P=0.02).
limitations
Small acute high-dose experiment, not individualized medicine instructions.
nutrient_topic
Calcium research collection; topical membership is not evidence of a direct dietary effect. · Calcium
organism
Homo sapiens
plain_language
The tested calcium preparation reduced the medicine reaching circulation.
primary_references
[cal-clin-singh2001] The acute effect of calcium carbonate on the intestinal absorption of levothyroxine (2001). https://pubmed.ncbi.nlm.nih.gov/11716045/ DOI: 10.1089/105072501753211046
tissue_or_cell_type
Human clinical or absorption endpoint
Calcium: mechanism-first literature curation (2026-09-17) · lines 1400–1410
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two visits separated by four weeks; serum-based pharmacokinetic estimation. · source_derived_draft · unverified_draft
### cal-carbonate-levothyroxine-absorption Simultaneous calcium carbonate reduced measured levothyroxine absorption in a seven-volunteer experiment. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The tested calcium preparation reduced the medicine reaching circulation. organism: Homo sapiens tissue_or_cell_type: Human clinical or absorption endpoint experimental_model: Two visits separated by four weeks; serum-based pharmacokinetic estimation. limitations: Small acute high-dose experiment, not individualized medicine instructions. exposure: 1000 micrograms levothyroxine with or without 2 g elemental calcium as carbonate; six-hour total absorption differed (P=0.02). [cal-clin-singh2001] The acute effect of calcium carbonate on the intestinal absorption of levothyroxine (2001). https://pubmed.ncbi.nlm.nih.gov/11716045/ DOI: 10.1089/105072501753211046
Complete structured claim and evidence
Pendrin abundance increased after 24 hours at 1 mM NaI; lower tested concentrations and 48-hour total abundance showed no significant increase.
Iodide ion → Rat pendrin / Slc26a4 source_derived_draftungraded
Experimental context and source evidence
experimental_model
Rat thyroid PCCl3 cells; 1 mM NaI unless specified.
exposure_category
Experimental iodide excess; normal is the schema category outside deficiency, machinery impairment and biomarker context.
limitations
Nonpolarized cells; concurrent changes do not establish pendrin necessity, human protection, or an intake threshold.
measurement
Western blot; Figure 1.
nutrient_topic
Iodine · Iodine
primary_references
Calil-Silveira et al. (2016). Iodide excess regulates its own efflux: a possible involvement of pendrin. DOI: 10.1152/ajpcell.00210.2015. https://pubmed.ncbi.nlm.nih.gov/26791486/
Iodine addendum: iodide excess and cellular export (2026-09-18) · lines 9–11
Calil-Silveira et al. (2016). Iodide excess regulates its own efflux: a possible involvement of pendrin. DOI: 10.1152/ajpcell.00210.2015. https://pubmed.ncbi.nlm.nih.gov/26791486/ · supports · Rat thyroid PCCl3 cells; 1 mM NaI unless specified. · source_derived_draft · unverified_draft
## abundance Pendrin abundance increased after 24 hours at 1 mM NaI; lower tested concentrations and 48-hour total abundance showed no significant increase. Measurement: Western blot; Figure 1.
Complete structured claim and evidence
Surface pendrin increased at 24 and 48 hours by flow cytometry; immunofluorescence also detected an increase at 12 hours.
Iodide ion → Rat pendrin / Slc26a4 source_derived_draftungraded
Experimental context and source evidence
experimental_model
Rat thyroid PCCl3 cells; 1 mM NaI unless specified.
exposure_category
Experimental iodide excess; normal is the schema category outside deficiency, machinery impairment and biomarker context.
limitations
Nonpolarized cells; concurrent changes do not establish pendrin necessity, human protection, or an intake threshold.
measurement
Nonpermeabilized staining; Figures 2–3.
nutrient_topic
Iodine · Iodine
primary_references
Calil-Silveira et al. (2016). Iodide excess regulates its own efflux: a possible involvement of pendrin. DOI: 10.1152/ajpcell.00210.2015. https://pubmed.ncbi.nlm.nih.gov/26791486/
Iodine addendum: iodide excess and cellular export (2026-09-18) · lines 13–15
Calil-Silveira et al. (2016). Iodide excess regulates its own efflux: a possible involvement of pendrin. DOI: 10.1152/ajpcell.00210.2015. https://pubmed.ncbi.nlm.nih.gov/26791486/ · supports · Rat thyroid PCCl3 cells; 1 mM NaI unless specified. · source_derived_draft · unverified_draft
## surface Surface pendrin increased at 24 and 48 hours by flow cytometry; immunofluorescence also detected an increase at 12 hours. Measurement: Nonpermeabilized staining; Figures 2–3.
Complete structured claim and evidence
Excess iodide slowed pendrin loss during cycloheximide treatment, supporting increased protein stability.
Iodide ion → Rat pendrin / Slc26a4 source_derived_draftungraded
Experimental context and source evidence
experimental_model
Rat thyroid PCCl3 cells; 1 mM NaI unless specified.
exposure_category
Experimental iodide excess; normal is the schema category outside deficiency, machinery impairment and biomarker context.
limitations
Nonpolarized cells; concurrent changes do not establish pendrin necessity, human protection, or an intake threshold.
measurement
Cycloheximide chase; Figure 4.
nutrient_topic
Iodine · Iodine
primary_references
Calil-Silveira et al. (2016). Iodide excess regulates its own efflux: a possible involvement of pendrin. DOI: 10.1152/ajpcell.00210.2015. https://pubmed.ncbi.nlm.nih.gov/26791486/
Iodine addendum: iodide excess and cellular export (2026-09-18) · lines 17–19
Calil-Silveira et al. (2016). Iodide excess regulates its own efflux: a possible involvement of pendrin. DOI: 10.1152/ajpcell.00210.2015. https://pubmed.ncbi.nlm.nih.gov/26791486/ · supports · Rat thyroid PCCl3 cells; 1 mM NaI unless specified. · source_derived_draft · unverified_draft
## stability Excess iodide slowed pendrin loss during cycloheximide treatment, supporting increased protein stability. Measurement: Cycloheximide chase; Figure 4.
Complete structured claim and evidence
Iodide pretreatment for 12, 24 and 48 hours increased fractional radioiodide efflux despite reduced iodide uptake.
Iodide ion → Cellular iodide efflux source_derived_draftungraded
Experimental context and source evidence
experimental_model
Rat thyroid PCCl3 cells; 1 mM NaI unless specified.
exposure_category
Experimental iodide excess; normal is the schema category outside deficiency, machinery impairment and biomarker context.
limitations
Nonpolarized cells; concurrent changes do not establish pendrin necessity, human protection, or an intake threshold.
measurement
Radioiodide release; perchlorate blocked reuptake; Figure 5B.
nutrient_topic
Iodine · Iodine
primary_references
Calil-Silveira et al. (2016). Iodide excess regulates its own efflux: a possible involvement of pendrin. DOI: 10.1152/ajpcell.00210.2015. https://pubmed.ncbi.nlm.nih.gov/26791486/
Iodine addendum: iodide excess and cellular export (2026-09-18) · lines 21–23
Calil-Silveira et al. (2016). Iodide excess regulates its own efflux: a possible involvement of pendrin. DOI: 10.1152/ajpcell.00210.2015. https://pubmed.ncbi.nlm.nih.gov/26791486/ · supports · Rat thyroid PCCl3 cells; 1 mM NaI unless specified. · source_derived_draft · unverified_draft
## efflux Iodide pretreatment for 12, 24 and 48 hours increased fractional radioiodide efflux despite reduced iodide uptake. Measurement: Radioiodide release; perchlorate blocked reuptake; Figure 5B.
Complete structured claim and evidence
Ano1 mRNA abundance did not significantly change after 24 hours of excess iodide.
Iodide ion → Rat Ano1 messenger RNA source_derived_draftungraded
Experimental context and source evidence
experimental_model
Rat thyroid PCCl3 cells; 1 mM NaI unless specified.
exposure_category
Experimental iodide excess; normal is the schema category outside deficiency, machinery impairment and biomarker context.
limitations
Nonpolarized cells; concurrent changes do not establish pendrin necessity, human protection, or an intake threshold.
measurement
Real-time PCR; Figure 6.
nutrient_topic
Iodine · Iodine
primary_references
Calil-Silveira et al. (2016). Iodide excess regulates its own efflux: a possible involvement of pendrin. DOI: 10.1152/ajpcell.00210.2015. https://pubmed.ncbi.nlm.nih.gov/26791486/
Iodine addendum: iodide excess and cellular export (2026-09-18) · lines 25–27
Calil-Silveira et al. (2016). Iodide excess regulates its own efflux: a possible involvement of pendrin. DOI: 10.1152/ajpcell.00210.2015. https://pubmed.ncbi.nlm.nih.gov/26791486/ · supports · Rat thyroid PCCl3 cells; 1 mM NaI unless specified. · source_derived_draft · unverified_draft
## ano1-null Ano1 mRNA abundance did not significantly change after 24 hours of excess iodide. Measurement: Real-time PCR; Figure 6.
Complete structured claim and evidence
Expression of cloned human NIS conferred perchlorate-sensitive iodide uptake on COS-7 cells.
Human sodium/iodide symporter / SLC5A5 → Cellular iodide uptake source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Human NIS cDNA expressed in COS-7 monkey cells
exposure
Transient human NIS cDNA expression; iodide and perchlorate concentrations not reported in the abstract.
limitations
Heterologous uptake establishes protein function, not whole-body iodine absorption.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Human protein in African green monkey cells
plain_language
Human NIS can bring iodide into cells.
primary_references
[iodine-trans-human-nis1996] Cloning of the human sodium lodide symporter. (1996). https://pubmed.ncbi.nlm.nih.gov/8806637/ DOI: 10.1006/bbrc.1996.1358
tissue_or_cell_type
COS-7 plasma membrane
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 154–165
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human NIS cDNA expressed in COS-7 monkey cells · source_derived_draft · unverified_draft
### iodine-trans-human-nis-uptake Expression of cloned human NIS conferred perchlorate-sensitive iodide uptake on COS-7 cells. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Human NIS can bring iodide into cells. organism: Human protein in African green monkey cells tissue_or_cell_type: COS-7 plasma membrane experimental_model: Human NIS cDNA expressed in COS-7 monkey cells limitations: Heterologous uptake establishes protein function, not whole-body iodine absorption. exposure: Transient human NIS cDNA expression; iodide and perchlorate concentrations not reported in the abstract. cross_nutrient: false [iodine-trans-human-nis1996] Cloning of the human sodium lodide symporter. (1996). https://pubmed.ncbi.nlm.nih.gov/8806637/ DOI: 10.1006/bbrc.1996.1358
Complete structured claim and evidence
Rat NIS expressed in Xenopus oocytes transported iodide with two sodium ions per anion and generated inward electrogenic transport.
Rat sodium/iodide symporter / Slc5a5 → NIS sodium-iodide cotransport source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
Rat NIS expressed in Xenopus laevis oocytes; electrophysiology and tracer uptake
exposure
Tracer uptake and electrophysiology; apparent sodium affinity 28 ± 3 mM and iodide affinity 33 ± 9 micromolar.
limitations
Rat-protein assay parameters are not dietary sodium requirements or human iodide thresholds.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Rat protein in Xenopus laevis oocytes
plain_language
NIS uses sodium movement to carry iodide into cells.
primary_references
[iodine-trans-stoichiometry1997] Thyroid Na+/I- symporter. Mechanism, stoichiometry, and specificity. (1997). https://pubmed.ncbi.nlm.nih.gov/9341168/ DOI: 10.1074/jbc.272.43.27230
tissue_or_cell_type
Oocyte plasma membrane
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 167–178
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat NIS expressed in Xenopus laevis oocytes; electrophysiology and tracer uptake · source_derived_draft · unverified_draft
### iodine-trans-sodium-coupling Rat NIS expressed in Xenopus oocytes transported iodide with two sodium ions per anion and generated inward electrogenic transport. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: NIS uses sodium movement to carry iodide into cells. organism: Rat protein in Xenopus laevis oocytes tissue_or_cell_type: Oocyte plasma membrane experimental_model: Rat NIS expressed in Xenopus laevis oocytes; electrophysiology and tracer uptake limitations: Rat-protein assay parameters are not dietary sodium requirements or human iodide thresholds. exposure: Tracer uptake and electrophysiology; apparent sodium affinity 28 ± 3 mM and iodide affinity 33 ± 9 micromolar. cross_nutrient: true [iodine-trans-stoichiometry1997] Thyroid Na+/I- symporter. Mechanism, stoichiometry, and specificity. (1997). https://pubmed.ncbi.nlm.nih.gov/9341168/ DOI: 10.1074/jbc.272.43.27230
Complete structured claim and evidence
Thermodynamic fits to rat IEC-6 NIS transport data estimated an iodide Kd of 224 micromolar without sodium binding and 22.4 micromolar in the sodium-bound state.
Sodium ion → NIS affinity for iodide source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
Endogenous rat NIS in IEC-6 intestinal epithelial cells; initial-rate transport and statistical thermodynamic fitting
exposure
Initial-rate iodide uptake at 5, 10, 20 or 60 micromolar iodide with 0–260 mM sodium; two-minute incubations; constant osmolarity.
limitations
Kd values depend on the authors’ transport model; the finding does not show that eating extra salt improves iodine status.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Rattus norvegicus
plain_language
Sodium binding makes NIS bind iodide more readily.
primary_references
[iodine-trans-sodium-affinity2014] Physiological sodium concentrations enhance the iodide affinity of the Na+/I- symporter. (2014). https://pubmed.ncbi.nlm.nih.gov/24888603/ DOI: 10.1038/ncomms4948
tissue_or_cell_type
IEC-6 intestinal epithelial cells
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 180–191
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Endogenous rat NIS in IEC-6 intestinal epithelial cells; initial-rate transport and statistical thermodynamic fitting · source_derived_draft · unverified_draft
### iodine-trans-sodium-affinity Thermodynamic fits to rat IEC-6 NIS transport data estimated an iodide Kd of 224 micromolar without sodium binding and 22.4 micromolar in the sodium-bound state. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Sodium binding makes NIS bind iodide more readily. organism: Rattus norvegicus tissue_or_cell_type: IEC-6 intestinal epithelial cells experimental_model: Endogenous rat NIS in IEC-6 intestinal epithelial cells; initial-rate transport and statistical thermodynamic fitting limitations: Kd values depend on the authors’ transport model; the finding does not show that eating extra salt improves iodine status. exposure: Initial-rate iodide uptake at 5, 10, 20 or 60 micromolar iodide with 0–260 mM sodium; two-minute incubations; constant osmolarity. cross_nutrient: true [iodine-trans-sodium-affinity2014] Physiological sodium concentrations enhance the iodide affinity of the Na+/I- symporter. (2014). https://pubmed.ncbi.nlm.nih.gov/24888603/ DOI: 10.1038/ncomms4948
Complete structured claim and evidence
The iodide-bound cryo-EM structure of engineered rat NIS contained density assigned to one iodide and two sodium ions in the substrate-binding cavity.
Tagged rat NIS N225Q/N485Q/N497Q → Iodide ion source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
Purified tagged unglycosylated rat NIS expressed in human 293F cells; cryo-EM and functional comparison
exposure
Tagged N225Q/N485Q/N497Q rat NIS; iodide-bound structure at 3.12 Å.
limitations
Structural ion assignments and engineered construct support a binding mechanism; they do not alone measure physiological transport rates.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Rat protein produced in human 293F cells
plain_language
The NIS structure shows where iodide and its two sodium partners bind.
primary_references
[iodine-trans-nis-structure2022] Structural insights into the mechanism of the sodium/iodide symporter. (2022). https://pubmed.ncbi.nlm.nih.gov/36517601/ DOI: 10.1038/s41586-022-05530-2
tissue_or_cell_type
Purified detergent-solubilized membrane protein
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 193–204
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified tagged unglycosylated rat NIS expressed in human 293F cells; cryo-EM and functional comparison · source_derived_draft · unverified_draft
### iodine-trans-nis-bound-ions The iodide-bound cryo-EM structure of engineered rat NIS contained density assigned to one iodide and two sodium ions in the substrate-binding cavity. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The NIS structure shows where iodide and its two sodium partners bind. organism: Rat protein produced in human 293F cells tissue_or_cell_type: Purified detergent-solubilized membrane protein experimental_model: Purified tagged unglycosylated rat NIS expressed in human 293F cells; cryo-EM and functional comparison limitations: Structural ion assignments and engineered construct support a binding mechanism; they do not alone measure physiological transport rates. exposure: Tagged N225Q/N485Q/N497Q rat NIS; iodide-bound structure at 3.12 Å. cross_nutrient: true [iodine-trans-nis-structure2022] Structural insights into the mechanism of the sodium/iodide symporter. (2022). https://pubmed.ncbi.nlm.nih.gov/36517601/ DOI: 10.1038/s41586-022-05530-2
Complete structured claim and evidence
Depletion of the AP-1B mu1B subunit in polarized MDCK cells caused expressed human NIS to be missorted toward the apical membrane while retaining transport function.
Canine AP-1B clathrin adaptor complex → NIS basolateral membrane targeting source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
false
experimental_model
Human NIS expressed in canine MDCK epithelial cells with AP-1 adaptor subunit silencing
exposure
AP-1B mu1B silencing compared with control MDCK-hNIS cells.
limitations
Engineered epithelial model; apical uptake does not establish useful blood-to-thyroid delivery in vivo.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Human NIS in canine MDCK cells
plain_language
Correct membrane placement depends on the cell’s sorting machinery.
primary_references
[iodine-trans-sorting2022] Basolateral Sorting of the Sodium/Iodide Symporter Is Mediated by Adaptor Protein 1 Clathrin Adaptor Complexes. (2022). https://pubmed.ncbi.nlm.nih.gov/35833460/ DOI: 10.1089/thy.2022.0163
tissue_or_cell_type
Polarized epithelial plasma membrane
trigger_kind
machinery_impairment Imported condition classification; unverified.
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 206–217
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human NIS expressed in canine MDCK epithelial cells with AP-1 adaptor subunit silencing · source_derived_draft · unverified_draft
### iodine-trans-ap1b-polarity Depletion of the AP-1B mu1B subunit in polarized MDCK cells caused expressed human NIS to be missorted toward the apical membrane while retaining transport function. Condition category: machinery_impairment nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Correct membrane placement depends on the cell’s sorting machinery. organism: Human NIS in canine MDCK cells tissue_or_cell_type: Polarized epithelial plasma membrane experimental_model: Human NIS expressed in canine MDCK epithelial cells with AP-1 adaptor subunit silencing limitations: Engineered epithelial model; apical uptake does not establish useful blood-to-thyroid delivery in vivo. exposure: AP-1B mu1B silencing compared with control MDCK-hNIS cells. cross_nutrient: false [iodine-trans-sorting2022] Basolateral Sorting of the Sodium/Iodide Symporter Is Mediated by Adaptor Protein 1 Clathrin Adaptor Complexes. (2022). https://pubmed.ncbi.nlm.nih.gov/35833460/ DOI: 10.1089/thy.2022.0163
Complete structured claim and evidence
Combined loss of AP-1A and AP-1B mu1 subunits reduced trafficking of human NIS to the MDCK cell plasma membrane.
Canine AP-1A clathrin adaptor complex → NIS delivery to the plasma membrane source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
false
experimental_model
Human NIS expressed in canine MDCK epithelial cells with AP-1 adaptor subunit silencing
exposure
Combined mu1A/mu1B depletion; comparison with single-subunit depletion and controls.
limitations
The experiment concerns protein delivery; it does not identify a dietary cofactor shortage.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Human NIS in canine MDCK cells
plain_language
Two adaptor systems together support delivery of NIS to the cell surface.
primary_references
[iodine-trans-sorting2022] Basolateral Sorting of the Sodium/Iodide Symporter Is Mediated by Adaptor Protein 1 Clathrin Adaptor Complexes. (2022). https://pubmed.ncbi.nlm.nih.gov/35833460/ DOI: 10.1089/thy.2022.0163
tissue_or_cell_type
Epithelial trans-Golgi/recycling-endosome trafficking
trigger_kind
machinery_impairment Imported condition classification; unverified.
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 219–230
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human NIS expressed in canine MDCK epithelial cells with AP-1 adaptor subunit silencing · source_derived_draft · unverified_draft
### iodine-trans-ap1-double-delivery Combined loss of AP-1A and AP-1B mu1 subunits reduced trafficking of human NIS to the MDCK cell plasma membrane. Condition category: machinery_impairment nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Two adaptor systems together support delivery of NIS to the cell surface. organism: Human NIS in canine MDCK cells tissue_or_cell_type: Epithelial trans-Golgi/recycling-endosome trafficking experimental_model: Human NIS expressed in canine MDCK epithelial cells with AP-1 adaptor subunit silencing limitations: The experiment concerns protein delivery; it does not identify a dietary cofactor shortage. exposure: Combined mu1A/mu1B depletion; comparison with single-subunit depletion and controls. cross_nutrient: false [iodine-trans-sorting2022] Basolateral Sorting of the Sodium/Iodide Symporter Is Mediated by Adaptor Protein 1 Clathrin Adaptor Complexes. (2022). https://pubmed.ncbi.nlm.nih.gov/35833460/ DOI: 10.1089/thy.2022.0163
Complete structured claim and evidence
Human NIS T354P expressed in COS-7 cells showed markedly reduced iodide uptake compared with normal NIS.
Human NIS p.Thr354Pro → Cellular iodide uptake source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
false
experimental_model
Human iodide-transport-defect patient and expression of patient-derived NIS in COS-7 cells
exposure
Patient-derived T354P cDNA expression; uptake concentration not provided in abstract.
limitations
The reported patient had goiter and defective accumulation but was essentially euthyroid; do not turn this case into universal hypothyroidism severity.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Human protein in African green monkey cells
plain_language
A defective NIS protein can limit uptake even when iodide is present.
primary_references
[iodine-trans-t354p1997] A homozygous missense mutation of the sodium/iodide symporter gene causing iodide transport defect. (1997). https://pubmed.ncbi.nlm.nih.gov/9398697/ DOI: 10.1210/jcem.82.12.4425
tissue_or_cell_type
COS-7 plasma membrane
trigger_kind
machinery_impairment Imported condition classification; unverified.
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 232–243
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human iodide-transport-defect patient and expression of patient-derived NIS in COS-7 cells · source_derived_draft · unverified_draft
### iodine-trans-t354p-uptake Human NIS T354P expressed in COS-7 cells showed markedly reduced iodide uptake compared with normal NIS. Condition category: machinery_impairment nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A defective NIS protein can limit uptake even when iodide is present. organism: Human protein in African green monkey cells tissue_or_cell_type: COS-7 plasma membrane experimental_model: Human iodide-transport-defect patient and expression of patient-derived NIS in COS-7 cells limitations: The reported patient had goiter and defective accumulation but was essentially euthyroid; do not turn this case into universal hypothyroidism severity. exposure: Patient-derived T354P cDNA expression; uptake concentration not provided in abstract. cross_nutrient: false [iodine-trans-t354p1997] A homozygous missense mutation of the sodium/iodide symporter gene causing iodide transport defect. (1997). https://pubmed.ncbi.nlm.nih.gov/9398697/ DOI: 10.1210/jcem.82.12.4425
Complete structured claim and evidence
NIS immunolocalization in rat small-intestinal enterocytes was restricted to their apical surface.
Rat sodium/iodide symporter / Slc5a5 → Intestinal epithelial apical membrane source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Rat and mouse intestinal localization, intestinal brush-border vesicles and IEC-6 cells
exposure
Tissue localization; no intake intervention used for this claim.
limitations
Anatomical localization does not quantify the fraction of human iodine absorbed through this route.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Rattus norvegicus
plain_language
In the intestine, NIS faces the dietary contents.
primary_references
[iodine-trans-intestine2009] The Na+/I- symporter mediates active iodide uptake in the intestine. (2009). https://pubmed.ncbi.nlm.nih.gov/19052257/ DOI: 10.1152/ajpcell.00509.2008
tissue_or_cell_type
Small-intestinal enterocytes
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 245–256
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat and mouse intestinal localization, intestinal brush-border vesicles and IEC-6 cells · source_derived_draft · unverified_draft
### iodine-trans-intestinal-location NIS immunolocalization in rat small-intestinal enterocytes was restricted to their apical surface. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: In the intestine, NIS faces the dietary contents. organism: Rattus norvegicus tissue_or_cell_type: Small-intestinal enterocytes experimental_model: Rat and mouse intestinal localization, intestinal brush-border vesicles and IEC-6 cells limitations: Anatomical localization does not quantify the fraction of human iodine absorbed through this route. exposure: Tissue localization; no intake intervention used for this claim. cross_nutrient: false [iodine-trans-intestine2009] The Na+/I- symporter mediates active iodide uptake in the intestine. (2009). https://pubmed.ncbi.nlm.nih.gov/19052257/ DOI: 10.1152/ajpcell.00509.2008
Complete structured claim and evidence
Rodent intestinal brush-border membrane vesicles accumulated iodide in a sodium-dependent, perchlorate-sensitive manner.
Sodium ion → Cellular iodide uptake source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
Rat and mouse intestinal localization, intestinal brush-border vesicles and IEC-6 cells
exposure
Sodium-dependent vesicle uptake with perchlorate inhibition; concentrations not verified from abstract.
limitations
The abstract does not assign every vesicle experiment to one rodent species; the claim preserves the rodent scope and does not attribute the protein to humans.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Rodent intestinal preparation; rat and mouse study
plain_language
Intestinal iodide uptake can use the sodium gradient.
primary_references
[iodine-trans-intestine2009] The Na+/I- symporter mediates active iodide uptake in the intestine. (2009). https://pubmed.ncbi.nlm.nih.gov/19052257/ DOI: 10.1152/ajpcell.00509.2008
tissue_or_cell_type
Intestinal brush-border membrane vesicles
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 258–269
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat and mouse intestinal localization, intestinal brush-border vesicles and IEC-6 cells · source_derived_draft · unverified_draft
### iodine-trans-intestinal-sodium-uptake Rodent intestinal brush-border membrane vesicles accumulated iodide in a sodium-dependent, perchlorate-sensitive manner. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Intestinal iodide uptake can use the sodium gradient. organism: Rodent intestinal preparation; rat and mouse study tissue_or_cell_type: Intestinal brush-border membrane vesicles experimental_model: Rat and mouse intestinal localization, intestinal brush-border vesicles and IEC-6 cells limitations: The abstract does not assign every vesicle experiment to one rodent species; the claim preserves the rodent scope and does not attribute the protein to humans. exposure: Sodium-dependent vesicle uptake with perchlorate inhibition; concentrations not verified from abstract. cross_nutrient: true [iodine-trans-intestine2009] The Na+/I- symporter mediates active iodide uptake in the intestine. (2009). https://pubmed.ncbi.nlm.nih.gov/19052257/ DOI: 10.1152/ajpcell.00509.2008
Complete structured claim and evidence
Mouse mammary Slc5a5 mRNA abundance increased during lactation.
Mammary lactation → Mouse Slc5a5 messenger RNA source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Lactating and comparator mouse mammary tissues; mouse NIS cDNA cloning
exposure
Lactating versus comparison mammary tissues; dietary doses not specified.
limitations
Transcript abundance is not a direct milk-transfer rate or evidence for a human supplement dose.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Mus musculus
plain_language
The lactating mouse mammary gland increases the transcript for the iodide transporter.
primary_references
[iodine-trans-lactation2001] Cloning of the mouse sodium iodide symporter and its expression in the mammary gland and other tissues. (2001). https://pubmed.ncbi.nlm.nih.gov/11431151/ DOI: 10.1677/joe.0.1700185
tissue_or_cell_type
Mammary gland
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 271–282
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Lactating and comparator mouse mammary tissues; mouse NIS cDNA cloning · source_derived_draft · unverified_draft
### iodine-trans-lactation-mrna Mouse mammary Slc5a5 mRNA abundance increased during lactation. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The lactating mouse mammary gland increases the transcript for the iodide transporter. organism: Mus musculus tissue_or_cell_type: Mammary gland experimental_model: Lactating and comparator mouse mammary tissues; mouse NIS cDNA cloning limitations: Transcript abundance is not a direct milk-transfer rate or evidence for a human supplement dose. exposure: Lactating versus comparison mammary tissues; dietary doses not specified. cross_nutrient: false [iodine-trans-lactation2001] Cloning of the mouse sodium iodide symporter and its expression in the mammary gland and other tissues. (2001). https://pubmed.ncbi.nlm.nih.gov/11431151/ DOI: 10.1677/joe.0.1700185
Complete structured claim and evidence
Human thyroid immunolocalization detected pendrin at the apical membrane in a subset of follicular epithelial cells.
Human pendrin / SLC26A4 → Thyrocyte apical membrane source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Human thyroid immunolocalization; separate rat FRTL-5 regulatory experiments
exposure
Peptide-specific antibody immunolocalization; thyroid specimens included Graves disease tissue.
limitations
Cell subset and tissue context matter; this does not establish pendrin as the only iodide exit route.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Homo sapiens
plain_language
Pendrin can face the thyroid’s hormone-making follicular space.
primary_references
[iodine-trans-pendrin-location2000] Pendrin, the protein encoded by the Pendred syndrome gene (PDS), is an apical porter of iodide in the thyroid and is regulated by thyroglobulin in FRTL-5 cells. (2000). https://pubmed.ncbi.nlm.nih.gov/10650967/ DOI: 10.1210/endo.141.2.7303
tissue_or_cell_type
Thyroid follicular epithelium
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 284–295
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human thyroid immunolocalization; separate rat FRTL-5 regulatory experiments · source_derived_draft · unverified_draft
### iodine-trans-pendrin-apical Human thyroid immunolocalization detected pendrin at the apical membrane in a subset of follicular epithelial cells. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Pendrin can face the thyroid’s hormone-making follicular space. organism: Homo sapiens tissue_or_cell_type: Thyroid follicular epithelium experimental_model: Human thyroid immunolocalization; separate rat FRTL-5 regulatory experiments limitations: Cell subset and tissue context matter; this does not establish pendrin as the only iodide exit route. exposure: Peptide-specific antibody immunolocalization; thyroid specimens included Graves disease tissue. cross_nutrient: false [iodine-trans-pendrin-location2000] Pendrin, the protein encoded by the Pendred syndrome gene (PDS), is an apical porter of iodide in the thyroid and is regulated by thyroglobulin in FRTL-5 cells. (2000). https://pubmed.ncbi.nlm.nih.gov/10650967/ DOI: 10.1210/endo.141.2.7303
Complete structured claim and evidence
Human pendrin expression supported iodide efflux in COS-7 and CHO mammalian-cell transport experiments.
Human pendrin / SLC26A4 → Cellular iodide efflux source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Human pendrin expressed in COS-7 and CHO cells with NIS; rat FRTL-5 comparison
exposure
Pendrin/NIS transfection; concentrations not provided in abstract.
limitations
Expression-cell data do not establish exclusive thyroid efflux control or transport specificity in every tissue.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Human protein in monkey COS-7 and hamster CHO cells
plain_language
Pendrin can let iodide leave cells.
primary_references
[iodine-trans-pendrin-efflux2002] Pendrin is an iodide-specific apical porter responsible for iodide efflux from thyroid cells. (2002). https://pubmed.ncbi.nlm.nih.gov/12107249/ DOI: 10.1210/jcem.87.7.8679
tissue_or_cell_type
Cultured-cell plasma membrane
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 297–308
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human pendrin expressed in COS-7 and CHO cells with NIS; rat FRTL-5 comparison · source_derived_draft · unverified_draft
### iodine-trans-pendrin-efflux Human pendrin expression supported iodide efflux in COS-7 and CHO mammalian-cell transport experiments. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Pendrin can let iodide leave cells. organism: Human protein in monkey COS-7 and hamster CHO cells tissue_or_cell_type: Cultured-cell plasma membrane experimental_model: Human pendrin expressed in COS-7 and CHO cells with NIS; rat FRTL-5 comparison limitations: Expression-cell data do not establish exclusive thyroid efflux control or transport specificity in every tissue. exposure: Pendrin/NIS transfection; concentrations not provided in abstract. cross_nutrient: false [iodine-trans-pendrin-efflux2002] Pendrin is an iodide-specific apical porter responsible for iodide efflux from thyroid cells. (2002). https://pubmed.ncbi.nlm.nih.gov/12107249/ DOI: 10.1210/jcem.87.7.8679
Complete structured claim and evidence
Expression of human pendrin increased chloride transport in Xenopus oocytes and Sf9 cells, alongside increased iodide transport.
Human pendrin / SLC26A4 → Chloride ion source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
Human pendrin expressed in Xenopus oocytes and Sf9 insect cells
exposure
PDS cRNA microinjection or recombinant baculovirus expression; concentrations not provided in abstract.
limitations
This demonstrates shared anion transport capability, not that dietary chloride deficiency blocks iodine repletion.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Human protein in Xenopus laevis and Spodoptera frugiperda cells
plain_language
Pendrin handles chloride as well as iodide.
primary_references
[iodine-trans-pendrin-halides1999] The Pendred syndrome gene encodes a chloride-iodide transport protein. (1999). https://pubmed.ncbi.nlm.nih.gov/10192399/ DOI: 10.1038/7783
tissue_or_cell_type
Heterologous cell membranes
transport_effect
depends Pendrin is an anion exchanger and the record reports increased transport without naming its direction.
transport_pool
the cytosol across the plasma membrane Pendrin is an anion exchanger and the record reports increased transport without naming its direction.
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 310–321
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human pendrin expressed in Xenopus oocytes and Sf9 insect cells · source_derived_draft · unverified_draft
### iodine-trans-pendrin-chloride Expression of human pendrin increased chloride transport in Xenopus oocytes and Sf9 cells, alongside increased iodide transport. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Pendrin handles chloride as well as iodide. organism: Human protein in Xenopus laevis and Spodoptera frugiperda cells tissue_or_cell_type: Heterologous cell membranes experimental_model: Human pendrin expressed in Xenopus oocytes and Sf9 insect cells limitations: This demonstrates shared anion transport capability, not that dietary chloride deficiency blocks iodine repletion. exposure: PDS cRNA microinjection or recombinant baculovirus expression; concentrations not provided in abstract. cross_nutrient: true [iodine-trans-pendrin-halides1999] The Pendred syndrome gene encodes a chloride-iodide transport protein. (1999). https://pubmed.ncbi.nlm.nih.gov/10192399/ DOI: 10.1038/7783
Complete structured claim and evidence
Ishii et al. detected human thyroid SLC26A7 staining predominantly on the apical side facing the follicular lumen.
Human SLC26A7 anion transporter → Thyrocyte apical membrane source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Human thyroid tissue; recombinant human SLC26A7 in Nthy, MDCK, COS-7 and HEK293T cells; two affected siblings
exposure
SLC26A7 immunofluorescence with NIS/pendrin localization comparisons; Fig. 1.
limitations
Other studies report basolateral localization; antibody, tissue and experimental context remain relevant.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Homo sapiens
plain_language
One human thyroid study placed SLC26A7 mainly toward the follicular space.
primary_references
[iodine-trans-slc26a7-2019] Congenital goitrous hypothyroidism is caused by dysfunction of the iodide transporter SLC26A7. (2019). https://pubmed.ncbi.nlm.nih.gov/31372509/ DOI: 10.1038/s42003-019-0503-6
tissue_or_cell_type
Thyroid follicular tissue
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 323–334
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human thyroid tissue; recombinant human SLC26A7 in Nthy, MDCK, COS-7 and HEK293T cells; two affected siblings · source_derived_draft · unverified_draft
### iodine-trans-a7-apical2019 Ishii et al. detected human thyroid SLC26A7 staining predominantly on the apical side facing the follicular lumen. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: One human thyroid study placed SLC26A7 mainly toward the follicular space. organism: Homo sapiens tissue_or_cell_type: Thyroid follicular tissue experimental_model: Human thyroid tissue; recombinant human SLC26A7 in Nthy, MDCK, COS-7 and HEK293T cells; two affected siblings limitations: Other studies report basolateral localization; antibody, tissue and experimental context remain relevant. exposure: SLC26A7 immunofluorescence with NIS/pendrin localization comparisons; Fig. 1. cross_nutrient: false [iodine-trans-slc26a7-2019] Congenital goitrous hypothyroidism is caused by dysfunction of the iodide transporter SLC26A7. (2019). https://pubmed.ncbi.nlm.nih.gov/31372509/ DOI: 10.1038/s42003-019-0503-6
Complete structured claim and evidence
MDCK monolayers coexpressing human NIS and SLC26A7 transferred more basal-chamber radioiodide into the apical chamber after 45 minutes than monolayers expressing NIS alone.
Human SLC26A7 anion transporter → Cellular iodide efflux source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Human thyroid tissue; recombinant human SLC26A7 in Nthy, MDCK, COS-7 and HEK293T cells; two affected siblings
exposure
Induced transporter expression 24 hours before assay; basal radioactive NaI and 45-minute transport readout; Fig. 3c.
limitations
A 2018 HEK293 efflux assay was negative. This experiment establishes capability under its conditions, not universal apical placement in human thyroid.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Human proteins in canine MDCK cells
plain_language
SLC26A7 increased iodide movement across a polarized cell sheet in this experiment.
primary_references
[iodine-trans-slc26a7-2019] Congenital goitrous hypothyroidism is caused by dysfunction of the iodide transporter SLC26A7. (2019). https://pubmed.ncbi.nlm.nih.gov/31372509/ DOI: 10.1038/s42003-019-0503-6
tissue_or_cell_type
Polarized epithelial bicameral culture
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 336–347
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human thyroid tissue; recombinant human SLC26A7 in Nthy, MDCK, COS-7 and HEK293T cells; two affected siblings · source_derived_draft · unverified_draft
### iodine-trans-a7-efflux2019 MDCK monolayers coexpressing human NIS and SLC26A7 transferred more basal-chamber radioiodide into the apical chamber after 45 minutes than monolayers expressing NIS alone. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: SLC26A7 increased iodide movement across a polarized cell sheet in this experiment. organism: Human proteins in canine MDCK cells tissue_or_cell_type: Polarized epithelial bicameral culture experimental_model: Human thyroid tissue; recombinant human SLC26A7 in Nthy, MDCK, COS-7 and HEK293T cells; two affected siblings limitations: A 2018 HEK293 efflux assay was negative. This experiment establishes capability under its conditions, not universal apical placement in human thyroid. exposure: Induced transporter expression 24 hours before assay; basal radioactive NaI and 45-minute transport readout; Fig. 3c. cross_nutrient: false [iodine-trans-slc26a7-2019] Congenital goitrous hypothyroidism is caused by dysfunction of the iodide transporter SLC26A7. (2019). https://pubmed.ncbi.nlm.nih.gov/31372509/ DOI: 10.1038/s42003-019-0503-6
Complete structured claim and evidence
Human SLC26A7 Q500Ter expressed in MDCK cells aggregated in the cytosol instead of showing the predominant surface localization of wild-type protein.
Human SLC26A7 p.Gln500Ter → SLC26A7 membrane localization source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
false
experimental_model
Human thyroid tissue; recombinant human SLC26A7 in Nthy, MDCK, COS-7 and HEK293T cells; two affected siblings
exposure
FLAG-tagged wild-type versus Q500Ter expression; immunofluorescence Fig. 5.
limitations
Tagged heterologous expression; localization and current loss are separate observations.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Human protein in canine MDCK cells
plain_language
This truncation prevents normal transporter placement.
primary_references
[iodine-trans-slc26a7-2019] Congenital goitrous hypothyroidism is caused by dysfunction of the iodide transporter SLC26A7. (2019). https://pubmed.ncbi.nlm.nih.gov/31372509/ DOI: 10.1038/s42003-019-0503-6
tissue_or_cell_type
Cell surface and cytosol
trigger_kind
machinery_impairment Imported condition classification; unverified.
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 349–360
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human thyroid tissue; recombinant human SLC26A7 in Nthy, MDCK, COS-7 and HEK293T cells; two affected siblings · source_derived_draft · unverified_draft
### iodine-trans-a7-q500-localization Human SLC26A7 Q500Ter expressed in MDCK cells aggregated in the cytosol instead of showing the predominant surface localization of wild-type protein. Condition category: machinery_impairment nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: This truncation prevents normal transporter placement. organism: Human protein in canine MDCK cells tissue_or_cell_type: Cell surface and cytosol experimental_model: Human thyroid tissue; recombinant human SLC26A7 in Nthy, MDCK, COS-7 and HEK293T cells; two affected siblings limitations: Tagged heterologous expression; localization and current loss are separate observations. exposure: FLAG-tagged wild-type versus Q500Ter expression; immunofluorescence Fig. 5. cross_nutrient: false [iodine-trans-slc26a7-2019] Congenital goitrous hypothyroidism is caused by dysfunction of the iodide transporter SLC26A7. (2019). https://pubmed.ncbi.nlm.nih.gov/31372509/ DOI: 10.1038/s42003-019-0503-6
Complete structured claim and evidence
Human SLC26A7 Q500Ter did not produce the wild-type enhancement of iodide-dependent current and iodide-sensitive fluorescence responses in HEK293T cells.
Human SLC26A7 p.Gln500Ter → SLC26A7 iodide conductance source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
false
experimental_model
Human thyroid tissue; recombinant human SLC26A7 in Nthy, MDCK, COS-7 and HEK293T cells; two affected siblings
exposure
Whole-cell electrophysiology and NaCl-to-NaI solution exchange; Figure 6; iodide-sensitive YFP readout.
limitations
These high-ion expression assays do not measure a physiological thyroid efflux rate; direction is determined by the imposed gradients.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Homo sapiens protein and HEK293T cells
plain_language
The truncated transporter failed the functional iodide-transport tests.
primary_references
[iodine-trans-slc26a7-2019] Congenital goitrous hypothyroidism is caused by dysfunction of the iodide transporter SLC26A7. (2019). https://pubmed.ncbi.nlm.nih.gov/31372509/ DOI: 10.1038/s42003-019-0503-6
tissue_or_cell_type
Cell plasma membrane
trigger_kind
machinery_impairment Imported condition classification; unverified.
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 362–373
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human thyroid tissue; recombinant human SLC26A7 in Nthy, MDCK, COS-7 and HEK293T cells; two affected siblings · source_derived_draft · unverified_draft
### iodine-trans-a7-q500-current Human SLC26A7 Q500Ter did not produce the wild-type enhancement of iodide-dependent current and iodide-sensitive fluorescence responses in HEK293T cells. Condition category: machinery_impairment nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The truncated transporter failed the functional iodide-transport tests. organism: Homo sapiens protein and HEK293T cells tissue_or_cell_type: Cell plasma membrane experimental_model: Human thyroid tissue; recombinant human SLC26A7 in Nthy, MDCK, COS-7 and HEK293T cells; two affected siblings limitations: These high-ion expression assays do not measure a physiological thyroid efflux rate; direction is determined by the imposed gradients. exposure: Whole-cell electrophysiology and NaCl-to-NaI solution exchange; Figure 6; iodide-sensitive YFP readout. cross_nutrient: false [iodine-trans-slc26a7-2019] Congenital goitrous hypothyroidism is caused by dysfunction of the iodide transporter SLC26A7. (2019). https://pubmed.ncbi.nlm.nih.gov/31372509/ DOI: 10.1038/s42003-019-0503-6
Complete structured claim and evidence
Cangul et al. found no enhancement of radioiodide efflux from HEK293 cells coexpressing human NIS and SLC26A7 compared with control cells, whereas pendrin enhanced efflux.
Human SLC26A7 anion transporter → Cellular iodide efflux source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Six human families, human SLC26A7/NIS-transfected HEK293 cells, Slc26a7-null mice
exposure
NIS plus SLC26A7, pendrin or control expression; time-dependent radioiodide efflux; five experiments, Fig. 2E.
limitations
A negative result in this assay is not proof that SLC26A7 never conducts iodide; later positive transport and structural evidence is retained.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Homo sapiens protein and HEK293 cells
plain_language
An earlier cell assay did not detect an iodide export effect from SLC26A7.
primary_references
[iodine-trans-slc26a7-2018] Homozygous loss-of-function mutations in SLC26A7 cause goitrous congenital hypothyroidism. (2018). https://pubmed.ncbi.nlm.nih.gov/30333321/ DOI: 10.1172/jci.insight.99631
tissue_or_cell_type
Cultured-cell plasma membrane
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 375–386
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Six human families, human SLC26A7/NIS-transfected HEK293 cells, Slc26a7-null mice · source_derived_draft · unverified_draft
### iodine-trans-a7-no-efflux2018 Cangul et al. found no enhancement of radioiodide efflux from HEK293 cells coexpressing human NIS and SLC26A7 compared with control cells, whereas pendrin enhanced efflux. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: An earlier cell assay did not detect an iodide export effect from SLC26A7. organism: Homo sapiens protein and HEK293 cells tissue_or_cell_type: Cultured-cell plasma membrane experimental_model: Six human families, human SLC26A7/NIS-transfected HEK293 cells, Slc26a7-null mice limitations: A negative result in this assay is not proof that SLC26A7 never conducts iodide; later positive transport and structural evidence is retained. exposure: NIS plus SLC26A7, pendrin or control expression; time-dependent radioiodide efflux; five experiments, Fig. 2E. cross_nutrient: false [iodine-trans-slc26a7-2018] Homozygous loss-of-function mutations in SLC26A7 cause goitrous congenital hypothyroidism. (2018). https://pubmed.ncbi.nlm.nih.gov/30333321/ DOI: 10.1172/jci.insight.99631
Complete structured claim and evidence
Homozygous truncating SLC26A7 variants segregated with goitrous congenital hypothyroidism in six unrelated families studied by Cangul et al.
Human SLC26A7 truncating pathogenic variants → Goitrous congenital hypothyroidism source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
false
experimental_model
Six human families, human SLC26A7/NIS-transfected HEK293 cells, Slc26a7-null mice
exposure
Six families with 13 affected individuals; molecular genetic characterization.
limitations
Genetic association establishes a machinery disorder, not low dietary iodine; precise physiological transport mechanism remained unresolved.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Homo sapiens
plain_language
Inherited SLC26A7 defects can disrupt thyroid hormone production.
primary_references
[iodine-trans-slc26a7-2018] Homozygous loss-of-function mutations in SLC26A7 cause goitrous congenital hypothyroidism. (2018). https://pubmed.ncbi.nlm.nih.gov/30333321/ DOI: 10.1172/jci.insight.99631
tissue_or_cell_type
Thyroid and whole-person clinical phenotype
trigger_kind
machinery_impairment Imported condition classification; unverified.
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 388–399
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Six human families, human SLC26A7/NIS-transfected HEK293 cells, Slc26a7-null mice · source_derived_draft · unverified_draft
### iodine-trans-a7-truncation-ch Homozygous truncating SLC26A7 variants segregated with goitrous congenital hypothyroidism in six unrelated families studied by Cangul et al. Condition category: machinery_impairment nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Inherited SLC26A7 defects can disrupt thyroid hormone production. organism: Homo sapiens tissue_or_cell_type: Thyroid and whole-person clinical phenotype experimental_model: Six human families, human SLC26A7/NIS-transfected HEK293 cells, Slc26a7-null mice limitations: Genetic association establishes a machinery disorder, not low dietary iodine; precise physiological transport mechanism remained unresolved. exposure: Six families with 13 affected individuals; molecular genetic characterization. cross_nutrient: false [iodine-trans-slc26a7-2018] Homozygous loss-of-function mutations in SLC26A7 cause goitrous congenital hypothyroidism. (2018). https://pubmed.ncbi.nlm.nih.gov/30333321/ DOI: 10.1172/jci.insight.99631
Complete structured claim and evidence
Perchlorate inhibited radioactive iodide uptake in CHO cells stably expressing human NIS.
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
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 401–412
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-perchlorate-inhibits Perchlorate 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
Thiocyanate inhibited radioactive iodide uptake in CHO cells stably expressing human NIS.
Thiocyanate 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 414–425
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-thiocyanate-inhibits Thiocyanate 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
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
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
Human SLC26A7 cryo-EM maps in the iodide-loaded state supported iodide assignments at a canonical site and a second site near the gate-domain interface.
Human SLC26A7 anion transporter → Iodide ion source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
Purified human SLC26A7 cryo-EM; recombinant human SLC26A7 in HEK293T cells with whole-cell patch clamp
exposure
Apo and iodide-loaded cryo-EM structures at approximately 3.2 and 3.1 Å; Fig. 2.
limitations
Binding-site structures support transport capability but do not establish apical versus basolateral thyroid localization.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Homo sapiens
plain_language
A recent structure directly supports iodide binding by human SLC26A7.
primary_references
[iodine-trans-slc26a7-structure2025] Structural basis for substrate recognition mechanism of human SLC26A7. (2025). https://pubmed.ncbi.nlm.nih.gov/40817112/ DOI: 10.1038/s41467-025-62792-w
tissue_or_cell_type
Purified membrane protein
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 453–464
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human SLC26A7 cryo-EM; recombinant human SLC26A7 in HEK293T cells with whole-cell patch clamp · source_derived_draft · unverified_draft
### iodine-trans-a7-bound-iodide2025 Human SLC26A7 cryo-EM maps in the iodide-loaded state supported iodide assignments at a canonical site and a second site near the gate-domain interface. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A recent structure directly supports iodide binding by human SLC26A7. organism: Homo sapiens tissue_or_cell_type: Purified membrane protein experimental_model: Purified human SLC26A7 cryo-EM; recombinant human SLC26A7 in HEK293T cells with whole-cell patch clamp limitations: Binding-site structures support transport capability but do not establish apical versus basolateral thyroid localization. exposure: Apo and iodide-loaded cryo-EM structures at approximately 3.2 and 3.1 Å; Fig. 2. cross_nutrient: true [iodine-trans-slc26a7-structure2025] Structural basis for substrate recognition mechanism of human SLC26A7. (2025). https://pubmed.ncbi.nlm.nih.gov/40817112/ DOI: 10.1038/s41467-025-62792-w
Complete structured claim and evidence
Human SLC26A7 expression in HEK293T cells generated chloride and iodide currents that increased when bath halide concentrations rose from 50 to 149 mM.
Human SLC26A7 anion transporter → Iodide ion source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
Purified human SLC26A7 cryo-EM; recombinant human SLC26A7 in HEK293T cells with whole-cell patch clamp
exposure
Whole-cell patch clamp 24 hours after 2 micrograms plasmid transfection; 50/149 mM total halide conditions; voltage steps from −100 to +100 mV.
limitations
Halide concentrations greatly exceed physiological iodide; transport capacity does not settle net thyroid iodide flux, stoichiometry or localization.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Homo sapiens
plain_language
Human SLC26A7 can carry both chloride and iodide under controlled laboratory conditions.
primary_references
[iodine-trans-slc26a7-structure2025] Structural basis for substrate recognition mechanism of human SLC26A7. (2025). https://pubmed.ncbi.nlm.nih.gov/40817112/ DOI: 10.1038/s41467-025-62792-w
tissue_or_cell_type
HEK293T plasma membrane
transport_effect
depends Recorded as a halide current that rose with bath halide concentration, so the direction follows the gradient.
transport_pool
the cytosol across the plasma membrane Recorded as a halide current that rose with bath halide concentration, so the direction follows the gradient.
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 466–477
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human SLC26A7 cryo-EM; recombinant human SLC26A7 in HEK293T cells with whole-cell patch clamp · source_derived_draft · unverified_draft
### iodine-trans-a7-halide-current2025 Human SLC26A7 expression in HEK293T cells generated chloride and iodide currents that increased when bath halide concentrations rose from 50 to 149 mM. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Human SLC26A7 can carry both chloride and iodide under controlled laboratory conditions. organism: Homo sapiens tissue_or_cell_type: HEK293T plasma membrane experimental_model: Purified human SLC26A7 cryo-EM; recombinant human SLC26A7 in HEK293T cells with whole-cell patch clamp limitations: Halide concentrations greatly exceed physiological iodide; transport capacity does not settle net thyroid iodide flux, stoichiometry or localization. exposure: Whole-cell patch clamp 24 hours after 2 micrograms plasmid transfection; 50/149 mM total halide conditions; voltage steps from −100 to +100 mV. cross_nutrient: true [iodine-trans-slc26a7-structure2025] Structural basis for substrate recognition mechanism of human SLC26A7. (2025). https://pubmed.ncbi.nlm.nih.gov/40817112/ DOI: 10.1038/s41467-025-62792-w
Complete structured claim and evidence
The 2026 Finnish SLC26A7 study reported basolateral SLC26A7 localization in human thyrocytes, with intense staining in hyperthyroid samples.
Human SLC26A7 anion transporter → Thyrocyte basolateral membrane source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Six human thyroid samples including two homozygous carriers, goitrous/hyperactive samples and controls; additional mouse models
exposure
Six human tissue samples spanning carriers, goitrous/hyperactive tissues and controls; abstract-level tissue localization result.
limitations
Small heterogeneous tissue set and abstract-only extraction; this differs from the 2019 apical result and does not prove all thyroid contexts share one location.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Homo sapiens
plain_language
A later human thyroid study placed SLC26A7 on the blood-facing side.
primary_references
[iodine-trans-slc26a7-localization2026] Finnish-Enriched SLC26A7 Variant in Congenital Hypothyroidism: Clinical Spectrum, Thyroid Histopathology, and Expression Analysis. (2026). https://pubmed.ncbi.nlm.nih.gov/41791885/ DOI: 10.1177/10507256251411983
tissue_or_cell_type
Human thyroid tissue
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 479–490
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Six human thyroid samples including two homozygous carriers, goitrous/hyperactive samples and controls; additional mouse models · source_derived_draft · unverified_draft
### iodine-trans-a7-basolateral2026 The 2026 Finnish SLC26A7 study reported basolateral SLC26A7 localization in human thyrocytes, with intense staining in hyperthyroid samples. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A later human thyroid study placed SLC26A7 on the blood-facing side. organism: Homo sapiens tissue_or_cell_type: Human thyroid tissue experimental_model: Six human thyroid samples including two homozygous carriers, goitrous/hyperactive samples and controls; additional mouse models limitations: Small heterogeneous tissue set and abstract-only extraction; this differs from the 2019 apical result and does not prove all thyroid contexts share one location. exposure: Six human tissue samples spanning carriers, goitrous/hyperactive tissues and controls; abstract-level tissue localization result. cross_nutrient: false [iodine-trans-slc26a7-localization2026] Finnish-Enriched SLC26A7 Variant in Congenital Hypothyroidism: Clinical Spectrum, Thyroid Histopathology, and Expression Analysis. (2026). https://pubmed.ncbi.nlm.nih.gov/41791885/ DOI: 10.1177/10507256251411983
Complete structured claim and evidence
Human DUOXA2 coexpression permitted DUOX2 ER-to-Golgi maturation and plasma-membrane delivery in a heterologous system.
Human dual oxidase maturation factor 2 → Human dual oxidase 2 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
evidence_span
{"source_cache": "artifacts/iodine-synthesis-sources/16651268.json", "json_field": "abstractText", "text_sha256": "9fa3bbca756141f9c8e8c334e58db29c97d930b117e5697ac91f28a0f41c92a0", "text_characters": 1357, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."}
experimental_model
Human DUOX2/DUOXA2 heterologous coexpression
exposure
DUOXA2 coexpression with DUOX2; doses not reported in abstract.
limitations
A reconstitution study; not a test of iodine intake.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Homo sapiens proteins; heterologous cells
plain_language
DUOXA2 helps the peroxide generator reach the cell surface.
primary_references
[iodine-syn-duoxa2006] Identification of the maturation factor for dual oxidase. Evolution of an eukaryotic operon equivalent. (2006). https://pubmed.ncbi.nlm.nih.gov/16651268/ DOI: 10.1074/jbc.c600095200
tissue_or_cell_type
ER, Golgi and plasma membrane
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 492–504
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human DUOX2/DUOXA2 heterologous coexpression · source_derived_draft · unverified_draft
### iodine-syn-duoxa-trafficking Human DUOXA2 coexpression permitted DUOX2 ER-to-Golgi maturation and plasma-membrane delivery in a heterologous system. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: DUOXA2 helps the peroxide generator reach the cell surface. organism: Homo sapiens proteins; heterologous cells tissue_or_cell_type: ER, Golgi and plasma membrane experimental_model: Human DUOX2/DUOXA2 heterologous coexpression limitations: A reconstitution study; not a test of iodine intake. exposure: DUOXA2 coexpression with DUOX2; doses not reported in abstract. cross_nutrient: false evidence_span: {"source_cache": "artifacts/iodine-synthesis-sources/16651268.json", "json_field": "abstractText", "text_sha256": "9fa3bbca756141f9c8e8c334e58db29c97d930b117e5697ac91f28a0f41c92a0", "text_characters": 1357, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."} [iodine-syn-duoxa2006] Identification of the maturation factor for dual oxidase. Evolution of an eukaryotic operon equivalent. (2006). https://pubmed.ncbi.nlm.nih.gov/16651268/ DOI: 10.1074/jbc.c600095200
Complete structured claim and evidence
Coexpressing DUOXA2 reconstituted functional human DUOX2-dependent hydrogen-peroxide generation.
Human dual oxidase maturation factor 2 → Hydrogen peroxide source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
evidence_span
{"source_cache": "artifacts/iodine-synthesis-sources/16651268.json", "json_field": "abstractText", "text_sha256": "9fa3bbca756141f9c8e8c334e58db29c97d930b117e5697ac91f28a0f41c92a0", "text_characters": 1357, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."}
experimental_model
Human DUOX2/DUOXA2 heterologous coexpression
exposure
Human DUOX2 with versus without DUOXA2.
limitations
Does not establish a dietary vitamin threshold.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Homo sapiens proteins; heterologous cells
plain_language
The maturation factor makes the peroxide-producing enzyme functional.
primary_references
[iodine-syn-duoxa2006] Identification of the maturation factor for dual oxidase. Evolution of an eukaryotic operon equivalent. (2006). https://pubmed.ncbi.nlm.nih.gov/16651268/ DOI: 10.1074/jbc.c600095200
tissue_or_cell_type
Cell surface
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 506–518
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human DUOX2/DUOXA2 heterologous coexpression · source_derived_draft · unverified_draft
### iodine-syn-duoxa-functional Coexpressing DUOXA2 reconstituted functional human DUOX2-dependent hydrogen-peroxide generation. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The maturation factor makes the peroxide-producing enzyme functional. organism: Homo sapiens proteins; heterologous cells tissue_or_cell_type: Cell surface experimental_model: Human DUOX2/DUOXA2 heterologous coexpression limitations: Does not establish a dietary vitamin threshold. exposure: Human DUOX2 with versus without DUOXA2. cross_nutrient: false evidence_span: {"source_cache": "artifacts/iodine-synthesis-sources/16651268.json", "json_field": "abstractText", "text_sha256": "9fa3bbca756141f9c8e8c334e58db29c97d930b117e5697ac91f28a0f41c92a0", "text_characters": 1357, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."} [iodine-syn-duoxa2006] Identification of the maturation factor for dual oxidase. Evolution of an eukaryotic operon equivalent. (2006). https://pubmed.ncbi.nlm.nih.gov/16651268/ DOI: 10.1074/jbc.c600095200
Complete structured claim and evidence
A homozygous truncating DUOX2 mutation accompanied a complete iodide-organification defect in the severe permanent case in the 2002 series.
Human DUOX2 truncating variant proteins studied in 2002 → Thyroid iodide organification source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
false
evidence_span
{"source_cache": "artifacts/iodine-synthesis-sources/12110737.json", "json_field": "abstractText", "text_sha256": "a0fa87eb7c584eb2b54cdc1de43ef65dd31bb4b7300f06c5b9ff4a8f703a151e", "text_characters": 1953, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."}
experimental_model
Sequencing of nine newborn-screened patients with iodide-organification defects and their relatives
exposure
Inherited DUOX2 truncation; no imposed dietary iodine restriction.
limitations
Small selected genetic series; no universal genotype-to-prognosis rule.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Homo sapiens
plain_language
A broken peroxide generator can prevent iodine from being incorporated into thyroid proteins.
primary_references
[iodine-syn-duox2002] Inactivating mutations in the gene for thyroid oxidase 2 (THOX2) and congenital hypothyroidism. (2002). https://pubmed.ncbi.nlm.nih.gov/12110737/ DOI: 10.1056/nejmoa012752
tissue_or_cell_type
Thyroid
trigger_kind
machinery_impairment Imported condition classification; unverified.
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 520–532
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Sequencing of nine newborn-screened patients with iodide-organification defects and their relatives · source_derived_draft · unverified_draft
### iodine-syn-duox2-organification A homozygous truncating DUOX2 mutation accompanied a complete iodide-organification defect in the severe permanent case in the 2002 series. Condition category: machinery_impairment nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A broken peroxide generator can prevent iodine from being incorporated into thyroid proteins. organism: Homo sapiens tissue_or_cell_type: Thyroid experimental_model: Sequencing of nine newborn-screened patients with iodide-organification defects and their relatives limitations: Small selected genetic series; no universal genotype-to-prognosis rule. exposure: Inherited DUOX2 truncation; no imposed dietary iodine restriction. cross_nutrient: false evidence_span: {"source_cache": "artifacts/iodine-synthesis-sources/12110737.json", "json_field": "abstractText", "text_sha256": "a0fa87eb7c584eb2b54cdc1de43ef65dd31bb4b7300f06c5b9ff4a8f703a151e", "text_characters": 1953, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."} [iodine-syn-duox2002] Inactivating mutations in the gene for thyroid oxidase 2 (THOX2) and congenital hypothyroidism. (2002). https://pubmed.ncbi.nlm.nih.gov/12110737/ DOI: 10.1056/nejmoa012752
Complete structured claim and evidence
Human DUOXA2 p.Y246X failed to reconstitute DUOX2 activity in vitro.
Human DUOXA2 p.Y246X truncation → Hydrogen peroxide source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
false
evidence_span
{"source_cache": "artifacts/iodine-synthesis-sources/18042646.json", "json_field": "abstractText", "text_sha256": "99a0667a0a4036b9ad94f59e6ba82a4c80c7f4b4228f11029f63db5c5b811da7", "text_characters": 1847, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."}
experimental_model
Human genetic case finding and heterologous DUOX2 reconstitution
exposure
Y246X mutant versus wild-type DUOXA2 in reconstitution.
limitations
Loss of enzyme machinery, not iodine or riboflavin shortage.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Homo sapiens proteins
plain_language
This truncated helper protein could not support peroxide production.
primary_references
[iodine-syn-duoxa2008] Biallelic inactivation of the dual oxidase maturation factor 2 (DUOXA2) gene as a novel cause of congenital hypothyroidism. (2008). https://pubmed.ncbi.nlm.nih.gov/18042646/ DOI: 10.1210/jc.2007-2020
tissue_or_cell_type
Heterologous cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 534–546
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human genetic case finding and heterologous DUOX2 reconstitution · source_derived_draft · unverified_draft
### iodine-syn-duoxa-mutant-function Human DUOXA2 p.Y246X failed to reconstitute DUOX2 activity in vitro. Condition category: machinery_impairment nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: This truncated helper protein could not support peroxide production. organism: Homo sapiens proteins tissue_or_cell_type: Heterologous cells experimental_model: Human genetic case finding and heterologous DUOX2 reconstitution limitations: Loss of enzyme machinery, not iodine or riboflavin shortage. exposure: Y246X mutant versus wild-type DUOXA2 in reconstitution. cross_nutrient: false evidence_span: {"source_cache": "artifacts/iodine-synthesis-sources/18042646.json", "json_field": "abstractText", "text_sha256": "99a0667a0a4036b9ad94f59e6ba82a4c80c7f4b4228f11029f63db5c5b811da7", "text_characters": 1847, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."} [iodine-syn-duoxa2008] Biallelic inactivation of the dual oxidase maturation factor 2 (DUOXA2) gene as a novel cause of congenital hypothyroidism. (2008). https://pubmed.ncbi.nlm.nih.gov/18042646/ DOI: 10.1210/jc.2007-2020
Complete structured claim and evidence
The homozygous DUOXA2 Y246X proband had congenital hypothyroidism with goiter and partial iodine-organification impairment.
Human DUOXA2 p.Y246X truncation → Dyshormonogenic hypothyroidism source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
false
evidence_span
{"source_cache": "artifacts/iodine-synthesis-sources/18042646.json", "json_field": "abstractText", "text_sha256": "99a0667a0a4036b9ad94f59e6ba82a4c80c7f4b4228f11029f63db5c5b811da7", "text_characters": 1847, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."}
experimental_model
Human genetic case finding and heterologous DUOX2 reconstitution
exposure
Inherited homozygous Y246X; no dietary manipulation.
limitations
Single proband; heterozygotes in the family were euthyroid.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Homo sapiens
plain_language
The enzyme-helper defect was linked to impaired hormone production from birth.
primary_references
[iodine-syn-duoxa2008] Biallelic inactivation of the dual oxidase maturation factor 2 (DUOXA2) gene as a novel cause of congenital hypothyroidism. (2008). https://pubmed.ncbi.nlm.nih.gov/18042646/ DOI: 10.1210/jc.2007-2020
tissue_or_cell_type
Thyroid
trigger_kind
machinery_impairment Imported condition classification; unverified.
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 548–560
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human genetic case finding and heterologous DUOX2 reconstitution · source_derived_draft · unverified_draft
### iodine-syn-duoxa-mutant-phenotype The homozygous DUOXA2 Y246X proband had congenital hypothyroidism with goiter and partial iodine-organification impairment. Condition category: machinery_impairment nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The enzyme-helper defect was linked to impaired hormone production from birth. organism: Homo sapiens tissue_or_cell_type: Thyroid experimental_model: Human genetic case finding and heterologous DUOX2 reconstitution limitations: Single proband; heterozygotes in the family were euthyroid. exposure: Inherited homozygous Y246X; no dietary manipulation. cross_nutrient: false evidence_span: {"source_cache": "artifacts/iodine-synthesis-sources/18042646.json", "json_field": "abstractText", "text_sha256": "99a0667a0a4036b9ad94f59e6ba82a4c80c7f4b4228f11029f63db5c5b811da7", "text_characters": 1847, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."} [iodine-syn-duoxa2008] Biallelic inactivation of the dual oxidase maturation factor 2 (DUOXA2) gene as a novel cause of congenital hypothyroidism. (2008). https://pubmed.ncbi.nlm.nih.gov/18042646/ DOI: 10.1210/jc.2007-2020
Complete structured claim and evidence
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.
Hemin → Human TPO ectodomain residues 1–848 source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
In CHO cells expressing human TPO, inhibition of heme biosynthesis by succinylacetone decreased surface TPO expression by approximately 80%.
Succinylacetone → Human thyroid peroxidase source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Exposing human TPO-expressing CHO cells to 10 micromolar H2O2 for 10 minutes increased cell-surface peroxidase activity by 65%.
Hydrogen peroxide → Human thyroid peroxidase source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Cryo-EM structures of the human TPO extracellular domain resolve heme at the peroxidase active site.
Human TPO ectodomain residues 1–839 → Heme source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Recombinant human TG produced a T4 signal after in-vitro iodination and proteolysis, whereas omission of iodide prevented the reaction.
Iodide ion → Tg derived t4 production source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
evidence_span
{"source_cache": "artifacts/iodine-synthesis-sources/32025030.txt", "start_char": 37603, "end_char": 38323, "text_sha256": "dfd7b409d46dbfe4e78cf481b6074477d36d70e14b5731f95a6b99ef0c43b33a", "text_characters": 720, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."}
experimental_model
Human TG cryo-EM, recombinant HEK293T-expressed TG and site-directed mutants
exposure
0.1 micromolar human TG, 1 mM KI, 24 mM glucose, 2 micrograms/mL glucose oxidase and 3 micrograms/mL lactoperoxidase; 10 minutes at 37 C followed by approximately 2.5 micrograms/mL Pronase and T4 ELISA. Most assays used lactoperoxidase after comparison with human TPO.
limitations
Artificial reaction with lactoperoxidase in most assays; not an intake-response curve.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Homo sapiens TG expressed in HEK293T cells
plain_language
Iodide supplies the iodine needed to build T4 on thyroglobulin.
primary_references
[iodine-syn-tg2020] The structure of human thyroglobulin. (2020). https://pubmed.ncbi.nlm.nih.gov/32025030/ DOI: 10.1038/s41586-020-1995-4
tissue_or_cell_type
Purified-protein reaction
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 618–630
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human TG cryo-EM, recombinant HEK293T-expressed TG and site-directed mutants · source_derived_draft · unverified_draft
### iodine-syn-tg-iodide-required Recombinant human TG produced a T4 signal after in-vitro iodination and proteolysis, whereas omission of iodide prevented the reaction. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Iodide supplies the iodine needed to build T4 on thyroglobulin. organism: Homo sapiens TG expressed in HEK293T cells tissue_or_cell_type: Purified-protein reaction experimental_model: Human TG cryo-EM, recombinant HEK293T-expressed TG and site-directed mutants limitations: Artificial reaction with lactoperoxidase in most assays; not an intake-response curve. exposure: 0.1 micromolar human TG, 1 mM KI, 24 mM glucose, 2 micrograms/mL glucose oxidase and 3 micrograms/mL lactoperoxidase; 10 minutes at 37 C followed by approximately 2.5 micrograms/mL Pronase and T4 ELISA. Most assays used lactoperoxidase after comparison with human TPO. cross_nutrient: false evidence_span: {"source_cache": "artifacts/iodine-synthesis-sources/32025030.txt", "start_char": 37603, "end_char": 38323, "text_sha256": "dfd7b409d46dbfe4e78cf481b6074477d36d70e14b5731f95a6b99ef0c43b33a", "text_characters": 720, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."} [iodine-syn-tg2020] The structure of human thyroglobulin. (2020). https://pubmed.ncbi.nlm.nih.gov/32025030/ DOI: 10.1038/s41586-020-1995-4
Complete structured claim and evidence
Replacing human TG acceptors Y24, Y2573, Y2766 and Y1310 with phenylalanine eliminated detectable T4 formation in the reconstituted assay.
Human TG four-acceptor Y-to-F mutant → Tg derived t4 production source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
evidence_span
{"source_cache": "artifacts/iodine-synthesis-sources/32025030.txt", "start_char": 8677, "end_char": 9897, "text_sha256": "fcdc18c2b096fdd24073329828fe9c6681e101b7f29bf985938e538faf6fb3fe", "text_characters": 1220, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."}
experimental_model
Human TG cryo-EM, recombinant HEK293T-expressed TG and site-directed mutants
exposure
0.1 micromolar human TG, 1 mM KI, 24 mM glucose, 2 micrograms/mL glucose oxidase and 3 micrograms/mL lactoperoxidase; 10 minutes at 37 C followed by approximately 2.5 micrograms/mL Pronase and T4 ELISA. Most assays used lactoperoxidase after comparison with human TPO. Four acceptor substitutions.
limitations
Engineered multi-site mutant; no human congenital phenotype inferred.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Homo sapiens TG
plain_language
Four hormone-forming acceptor sites account for the measured T4 production.
primary_references
[iodine-syn-tg2020] The structure of human thyroglobulin. (2020). https://pubmed.ncbi.nlm.nih.gov/32025030/ DOI: 10.1038/s41586-020-1995-4
tissue_or_cell_type
Purified-protein reaction
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 632–644
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human TG cryo-EM, recombinant HEK293T-expressed TG and site-directed mutants · source_derived_draft · unverified_draft
### iodine-syn-tg-acceptor-mutants Replacing human TG acceptors Y24, Y2573, Y2766 and Y1310 with phenylalanine eliminated detectable T4 formation in the reconstituted assay. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Four hormone-forming acceptor sites account for the measured T4 production. organism: Homo sapiens TG tissue_or_cell_type: Purified-protein reaction experimental_model: Human TG cryo-EM, recombinant HEK293T-expressed TG and site-directed mutants limitations: Engineered multi-site mutant; no human congenital phenotype inferred. exposure: 0.1 micromolar human TG, 1 mM KI, 24 mM glucose, 2 micrograms/mL glucose oxidase and 3 micrograms/mL lactoperoxidase; 10 minutes at 37 C followed by approximately 2.5 micrograms/mL Pronase and T4 ELISA. Most assays used lactoperoxidase after comparison with human TPO. Four acceptor substitutions. cross_nutrient: false evidence_span: {"source_cache": "artifacts/iodine-synthesis-sources/32025030.txt", "start_char": 8677, "end_char": 9897, "text_sha256": "fcdc18c2b096fdd24073329828fe9c6681e101b7f29bf985938e538faf6fb3fe", "text_characters": 1220, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."} [iodine-syn-tg2020] The structure of human thyroglobulin. (2020). https://pubmed.ncbi.nlm.nih.gov/32025030/ DOI: 10.1038/s41586-020-1995-4
Complete structured claim and evidence
Replacing human TG donor residues Y2540, Y2766, Y108, Y234 and Y149 with phenylalanine suppressed significant T4 synthesis.
Human TG five-donor Y-to-F mutant → Tg derived t4 production source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
evidence_span
{"source_cache": "artifacts/iodine-synthesis-sources/32025030.txt", "start_char": 9120, "end_char": 9940, "text_sha256": "8b8cd3eb09e3950bb40977268ed2a95e242386b632a9d45ccd8a2e156aead2b1", "text_characters": 820, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."}
experimental_model
Human TG cryo-EM, recombinant HEK293T-expressed TG and site-directed mutants
exposure
0.1 micromolar human TG, 1 mM KI, 24 mM glucose, 2 micrograms/mL glucose oxidase and 3 micrograms/mL lactoperoxidase; 10 minutes at 37 C followed by approximately 2.5 micrograms/mL Pronase and T4 ELISA. Most assays used lactoperoxidase after comparison with human TPO. Five donor substitutions.
limitations
Multi-site mutagenesis supports the donor set; not an isolated rate for every individual site.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Homo sapiens TG
plain_language
The paired donor tyrosines are also needed to assemble T4.
primary_references
[iodine-syn-tg2020] The structure of human thyroglobulin. (2020). https://pubmed.ncbi.nlm.nih.gov/32025030/ DOI: 10.1038/s41586-020-1995-4
tissue_or_cell_type
Purified-protein reaction
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 646–658
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human TG cryo-EM, recombinant HEK293T-expressed TG and site-directed mutants · source_derived_draft · unverified_draft
### iodine-syn-tg-donor-mutants Replacing human TG donor residues Y2540, Y2766, Y108, Y234 and Y149 with phenylalanine suppressed significant T4 synthesis. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The paired donor tyrosines are also needed to assemble T4. organism: Homo sapiens TG tissue_or_cell_type: Purified-protein reaction experimental_model: Human TG cryo-EM, recombinant HEK293T-expressed TG and site-directed mutants limitations: Multi-site mutagenesis supports the donor set; not an isolated rate for every individual site. exposure: 0.1 micromolar human TG, 1 mM KI, 24 mM glucose, 2 micrograms/mL glucose oxidase and 3 micrograms/mL lactoperoxidase; 10 minutes at 37 C followed by approximately 2.5 micrograms/mL Pronase and T4 ELISA. Most assays used lactoperoxidase after comparison with human TPO. Five donor substitutions. cross_nutrient: false evidence_span: {"source_cache": "artifacts/iodine-synthesis-sources/32025030.txt", "start_char": 9120, "end_char": 9940, "text_sha256": "8b8cd3eb09e3950bb40977268ed2a95e242386b632a9d45ccd8a2e156aead2b1", "text_characters": 820, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."} [iodine-syn-tg2020] The structure of human thyroglobulin. (2020). https://pubmed.ncbi.nlm.nih.gov/32025030/ DOI: 10.1038/s41586-020-1995-4
Complete structured claim and evidence
Human thyroid lysosomal extracts cleaved radioiodinated rabbit TG into discrete iodine-bearing peptides before iodoamino-acid release.
Rabbit thyroglobulin → Thyroglobulin iodopeptide formation source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
evidence_span
{"source_cache": "artifacts/iodine-synthesis-sources/1903699.json", "json_field": "abstractText", "text_sha256": "2fecda8478b67ba815425948ac7198157a2d0e8fe18381b9bf3a9fd0e5190410", "text_characters": 2209, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."}
experimental_model
In-vivo-radioiodinated rabbit TG incubated with human thyroid lysosomal extracts and protease inhibitors
exposure
Rabbit [125I]TG with human thyroid lysosomal extracts: 20–45 minutes for peptides; 8 and 24 hours for iodoamino-acid release.
limitations
Mixed-species cell-free system; precursor proteolysis is not equivalent to circulating hormone secretion.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Oryctolagus cuniculus substrate; Homo sapiens lysosomal extracts
plain_language
Thyroglobulin is first cut into smaller hormone-containing fragments.
primary_references
[iodine-syn-lysosome1991] Proteolytic processing of thyroglobulin by extracts of thyroid lysosomes. (1991). https://pubmed.ncbi.nlm.nih.gov/1903699/ DOI: 10.1210/endo-128-6-3073
tissue_or_cell_type
Human thyroid lysosomal extracts
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 660–672
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · In-vivo-radioiodinated rabbit TG incubated with human thyroid lysosomal extracts and protease inhibitors · source_derived_draft · unverified_draft
### iodine-syn-lysosomal-fragments Human thyroid lysosomal extracts cleaved radioiodinated rabbit TG into discrete iodine-bearing peptides before iodoamino-acid release. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Thyroglobulin is first cut into smaller hormone-containing fragments. organism: Oryctolagus cuniculus substrate; Homo sapiens lysosomal extracts tissue_or_cell_type: Human thyroid lysosomal extracts experimental_model: In-vivo-radioiodinated rabbit TG incubated with human thyroid lysosomal extracts and protease inhibitors limitations: Mixed-species cell-free system; precursor proteolysis is not equivalent to circulating hormone secretion. exposure: Rabbit [125I]TG with human thyroid lysosomal extracts: 20–45 minutes for peptides; 8 and 24 hours for iodoamino-acid release. cross_nutrient: false evidence_span: {"source_cache": "artifacts/iodine-synthesis-sources/1903699.json", "json_field": "abstractText", "text_sha256": "2fecda8478b67ba815425948ac7198157a2d0e8fe18381b9bf3a9fd0e5190410", "text_characters": 2209, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."} [iodine-syn-lysosome1991] Proteolytic processing of thyroglobulin by extracts of thyroid lysosomes. (1991). https://pubmed.ncbi.nlm.nih.gov/1903699/ DOI: 10.1210/endo-128-6-3073
Complete structured claim and evidence
Combined inhibition of cathepsins B, D and L reduced long-incubation iodoamino-acid release from radioiodinated rabbit TG by 80–90%.
Experimental cathepsin B/D/L inhibitor combination → Lysosomal iodoamino acid release source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
evidence_span
{"source_cache": "artifacts/iodine-synthesis-sources/1903699.json", "json_field": "abstractText", "text_sha256": "2fecda8478b67ba815425948ac7198157a2d0e8fe18381b9bf3a9fd0e5190410", "text_characters": 2209, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."}
experimental_model
In-vivo-radioiodinated rabbit TG incubated with human thyroid lysosomal extracts and protease inhibitors
exposure
Rabbit [125I]TG with human thyroid lysosomal extracts: 20–45 minutes for peptides; 8 and 24 hours for iodoamino-acid release. Combined protease inhibition.
limitations
Iodoamino-acid endpoint includes iodothyronines and iodotyrosines; do not assign the percentage specifically to T4.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Oryctolagus cuniculus substrate; Homo sapiens enzymes
plain_language
Blocking these proteases greatly reduced release of iodinated amino acids from TG.
primary_references
[iodine-syn-lysosome1991] Proteolytic processing of thyroglobulin by extracts of thyroid lysosomes. (1991). https://pubmed.ncbi.nlm.nih.gov/1903699/ DOI: 10.1210/endo-128-6-3073
tissue_or_cell_type
Human thyroid lysosomal extracts
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 674–686
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · In-vivo-radioiodinated rabbit TG incubated with human thyroid lysosomal extracts and protease inhibitors · source_derived_draft · unverified_draft
### iodine-syn-lysosomal-inhibition Combined inhibition of cathepsins B, D and L reduced long-incubation iodoamino-acid release from radioiodinated rabbit TG by 80–90%. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Blocking these proteases greatly reduced release of iodinated amino acids from TG. organism: Oryctolagus cuniculus substrate; Homo sapiens enzymes tissue_or_cell_type: Human thyroid lysosomal extracts experimental_model: In-vivo-radioiodinated rabbit TG incubated with human thyroid lysosomal extracts and protease inhibitors limitations: Iodoamino-acid endpoint includes iodothyronines and iodotyrosines; do not assign the percentage specifically to T4. exposure: Rabbit [125I]TG with human thyroid lysosomal extracts: 20–45 minutes for peptides; 8 and 24 hours for iodoamino-acid release. Combined protease inhibition. cross_nutrient: false evidence_span: {"source_cache": "artifacts/iodine-synthesis-sources/1903699.json", "json_field": "abstractText", "text_sha256": "2fecda8478b67ba815425948ac7198157a2d0e8fe18381b9bf3a9fd0e5190410", "text_characters": 2209, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."} [iodine-syn-lysosome1991] Proteolytic processing of thyroglobulin by extracts of thyroid lysosomes. (1991). https://pubmed.ncbi.nlm.nih.gov/1903699/ DOI: 10.1210/endo-128-6-3073
Complete structured claim and evidence
Purified soluble human IYD released radiolabeled iodide from diiodotyrosine during reductive enzyme assays.
Human IYD lacking N-terminal membrane anchor → Iodide ion source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_span
{"source_cache": "artifacts/iodine-synthesis-sources/25395621.txt", "start_char": 11103, "end_char": 12723, "text_sha256": "726c34262182d49a45a4741a29a49ef70bf6d529c79d75cfbb0e9ea59ffd256b", "text_characters": 1620, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."}
experimental_model
Recombinant human IYD lacking residues 1–31; crystallography, radiotracer kinetics and redox titration
exposure
0–70 micromolar [125I]DIT; sodium dithionite supplies reducing equivalents.
limitations
Anchor-deleted enzyme and artificial reductant; does not identify the physiological electron donor.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Homo sapiens recombinant protein
plain_language
IYD recovers iodine from leftover iodinated tyrosine.
primary_references
[iodine-syn-iyd2015] A switch between one- and two-electron chemistry of the human flavoprotein iodotyrosine deiodinase is controlled by substrate. (2015). https://pubmed.ncbi.nlm.nih.gov/25395621/ DOI: 10.1074/jbc.m114.605964
tissue_or_cell_type
Purified soluble IYD
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 688–700
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human IYD lacking residues 1–31; crystallography, radiotracer kinetics and redox titration · source_derived_draft · unverified_draft
### iodine-syn-iyd-dit-salvage Purified soluble human IYD released radiolabeled iodide from diiodotyrosine during reductive enzyme assays. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: IYD recovers iodine from leftover iodinated tyrosine. organism: Homo sapiens recombinant protein tissue_or_cell_type: Purified soluble IYD experimental_model: Recombinant human IYD lacking residues 1–31; crystallography, radiotracer kinetics and redox titration limitations: Anchor-deleted enzyme and artificial reductant; does not identify the physiological electron donor. exposure: 0–70 micromolar [125I]DIT; sodium dithionite supplies reducing equivalents. cross_nutrient: true evidence_span: {"source_cache": "artifacts/iodine-synthesis-sources/25395621.txt", "start_char": 11103, "end_char": 12723, "text_sha256": "726c34262182d49a45a4741a29a49ef70bf6d529c79d75cfbb0e9ea59ffd256b", "text_characters": 1620, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."} [iodine-syn-iyd2015] A switch between one- and two-electron chemistry of the human flavoprotein iodotyrosine deiodinase is controlled by substrate. (2015). https://pubmed.ncbi.nlm.nih.gov/25395621/ DOI: 10.1074/jbc.m114.605964
Complete structured claim and evidence
Human IYD crystal structures show one bound FMN per polypeptide, with iodotyrosine contacting its isoalloxazine ring in the substrate complex.
Human IYD lacking N-terminal membrane anchor → Flavin mononucleotide source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_span
{"source_cache": "artifacts/iodine-synthesis-sources/25395621.txt", "start_char": 14596, "end_char": 15366, "text_sha256": "5f3959109e358adaddae3ea78c716d16316c28f6fb4153ad5696bae7b1ed733e", "text_characters": 770, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."}
experimental_model
Recombinant human IYD lacking residues 1–31; crystallography, radiotracer kinetics and redox titration
exposure
Human soluble IYD crystallized alone or with 3-iodo-L-tyrosine.
limitations
Cofactor structure; no riboflavin restriction or supplementation study.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Homo sapiens recombinant protein
plain_language
IYD uses the vitamin-B2-derived cofactor FMN to handle iodotyrosine.
primary_references
[iodine-syn-iyd2015] A switch between one- and two-electron chemistry of the human flavoprotein iodotyrosine deiodinase is controlled by substrate. (2015). https://pubmed.ncbi.nlm.nih.gov/25395621/ DOI: 10.1074/jbc.m114.605964
tissue_or_cell_type
Purified soluble IYD
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 702–714
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human IYD lacking residues 1–31; crystallography, radiotracer kinetics and redox titration · source_derived_draft · unverified_draft
### iodine-syn-iyd-fmn-binding Human IYD crystal structures show one bound FMN per polypeptide, with iodotyrosine contacting its isoalloxazine ring in the substrate complex. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: IYD uses the vitamin-B2-derived cofactor FMN to handle iodotyrosine. organism: Homo sapiens recombinant protein tissue_or_cell_type: Purified soluble IYD experimental_model: Recombinant human IYD lacking residues 1–31; crystallography, radiotracer kinetics and redox titration limitations: Cofactor structure; no riboflavin restriction or supplementation study. exposure: Human soluble IYD crystallized alone or with 3-iodo-L-tyrosine. cross_nutrient: true evidence_span: {"source_cache": "artifacts/iodine-synthesis-sources/25395621.txt", "start_char": 14596, "end_char": 15366, "text_sha256": "5f3959109e358adaddae3ea78c716d16316c28f6fb4153ad5696bae7b1ed733e", "text_characters": 770, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."} [iodine-syn-iyd2015] A switch between one- and two-electron chemistry of the human flavoprotein iodotyrosine deiodinase is controlled by substrate. (2015). https://pubmed.ncbi.nlm.nih.gov/25395621/ DOI: 10.1074/jbc.m114.605964
Complete structured claim and evidence
The substrate analog 3-fluoro-L-tyrosine stabilized a one-electron-reduced FMN semiquinone during reductive titration of soluble human IYD.
3-Fluoro-L-tyrosine → FMN semiquinone source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_span
{"source_cache": "artifacts/iodine-synthesis-sources/25395621.txt", "start_char": 4223, "end_char": 4943, "text_sha256": "5567eccc06be2559ce51e8a2640697678a8fd3c1216896997568a9341da5a73b", "text_characters": 720, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."}
experimental_model
Recombinant human IYD lacking residues 1–31; crystallography, radiotracer kinetics and redox titration
exposure
Reductive titration with versus without active-site ligand.
limitations
An inert fluorotyrosine probe demonstrates cofactor control, not physiological fluoride displacement.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Homo sapiens recombinant protein
plain_language
Substrate-like binding changes which FMN redox state the enzyme can stabilize.
primary_references
[iodine-syn-iyd2015] A switch between one- and two-electron chemistry of the human flavoprotein iodotyrosine deiodinase is controlled by substrate. (2015). https://pubmed.ncbi.nlm.nih.gov/25395621/ DOI: 10.1074/jbc.m114.605964
tissue_or_cell_type
Purified soluble IYD
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 716–728
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human IYD lacking residues 1–31; crystallography, radiotracer kinetics and redox titration · source_derived_draft · unverified_draft
### iodine-syn-iyd-redox-switch The substrate analog 3-fluoro-L-tyrosine stabilized a one-electron-reduced FMN semiquinone during reductive titration of soluble human IYD. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Substrate-like binding changes which FMN redox state the enzyme can stabilize. organism: Homo sapiens recombinant protein tissue_or_cell_type: Purified soluble IYD experimental_model: Recombinant human IYD lacking residues 1–31; crystallography, radiotracer kinetics and redox titration limitations: An inert fluorotyrosine probe demonstrates cofactor control, not physiological fluoride displacement. exposure: Reductive titration with versus without active-site ligand. cross_nutrient: true evidence_span: {"source_cache": "artifacts/iodine-synthesis-sources/25395621.txt", "start_char": 4223, "end_char": 4943, "text_sha256": "5567eccc06be2559ce51e8a2640697678a8fd3c1216896997568a9341da5a73b", "text_characters": 720, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."} [iodine-syn-iyd2015] A switch between one- and two-electron chemistry of the human flavoprotein iodotyrosine deiodinase is controlled by substrate. (2015). https://pubmed.ncbi.nlm.nih.gov/25395621/ DOI: 10.1074/jbc.m114.605964
Complete structured claim and evidence
Replacing FMN with 2-prime-deoxyFMN in human IYD lowered iodotyrosine dehalogenation efficiency by more than fivefold while increasing turnover number by more than sixfold.
2-prime-Deoxy-FMN → Iyd catalytic efficiency source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_span
{"source_cache": "artifacts/iodine-synthesis-sources/37654510.txt", "start_char": 9069, "end_char": 10489, "text_sha256": "5e0dc84da55832b58d1a1ad6c3a327551b878ef108389abf34b7eda4dcc8b7a1", "text_characters": 1420, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."}
experimental_model
Purified soluble human IYD reconstituted with FMN or synthetic 2-prime-deoxyFMN
exposure
Human IYD reconstituted with FMN or synthetic 2-prime-deoxyFMN; Table 1 kcat/Km 5.0 versus 0.97 x 10^3 M^-1 s^-1; kcat 0.052 versus 0.32 s^-1.
limitations
Synthetic cofactor substitution is not riboflavin deficiency; kcat/Km and kcat are different measurements. Table 1 native-FMN kinetic comparator is cited from previous work; reconstituted FMN was used for binding comparisons.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Homo sapiens recombinant protein
plain_language
A small change to FMN weakened overall substrate processing even though the saturated enzyme turned over faster.
primary_references
[iodine-syn-iyd2023] The 2'-hydroxy group of flavin mononucleotide influences the catalytic function and promiscuity of the flavoprotein iodotyrosine dehalogenase. (2023). https://pubmed.ncbi.nlm.nih.gov/37654510/ DOI: 10.1039/d3cb00094j
tissue_or_cell_type
Purified enzyme
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 730–742
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified soluble human IYD reconstituted with FMN or synthetic 2-prime-deoxyFMN · source_derived_draft · unverified_draft
### iodine-syn-iyd-cofactor-substitution Replacing FMN with 2-prime-deoxyFMN in human IYD lowered iodotyrosine dehalogenation efficiency by more than fivefold while increasing turnover number by more than sixfold. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A small change to FMN weakened overall substrate processing even though the saturated enzyme turned over faster. organism: Homo sapiens recombinant protein tissue_or_cell_type: Purified enzyme experimental_model: Purified soluble human IYD reconstituted with FMN or synthetic 2-prime-deoxyFMN limitations: Synthetic cofactor substitution is not riboflavin deficiency; kcat/Km and kcat are different measurements. Table 1 native-FMN kinetic comparator is cited from previous work; reconstituted FMN was used for binding comparisons. exposure: Human IYD reconstituted with FMN or synthetic 2-prime-deoxyFMN; Table 1 kcat/Km 5.0 versus 0.97 x 10^3 M^-1 s^-1; kcat 0.052 versus 0.32 s^-1. cross_nutrient: true evidence_span: {"source_cache": "artifacts/iodine-synthesis-sources/37654510.txt", "start_char": 9069, "end_char": 10489, "text_sha256": "5e0dc84da55832b58d1a1ad6c3a327551b878ef108389abf34b7eda4dcc8b7a1", "text_characters": 1420, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."} [iodine-syn-iyd2023] The 2'-hydroxy group of flavin mononucleotide influences the catalytic function and promiscuity of the flavoprotein iodotyrosine dehalogenase. (2023). https://pubmed.ncbi.nlm.nih.gov/37654510/ DOI: 10.1039/d3cb00094j
Complete structured claim and evidence
The IYD variants identified in four affected patients showed markedly reduced iodotyrosine-deiodinase activity in vitro.
Human IYD patient variant proteins studied in 2008 → Iodotyrosine deiodination source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
true
evidence_span
{"source_cache": "artifacts/iodine-synthesis-sources/18434651.json", "json_field": "abstractText", "text_sha256": "f257956854445e268691cd3df1388ca16cea3f41320a48753df200a381c56431", "text_characters": 914, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."}
experimental_model
Four selected patients from three unrelated families plus in-vitro mutant enzyme assays
exposure
Two missense variants and one three-base-pair deletion; no nutrient-restriction experiment.
limitations
Abstract does not provide exact variant residues or assay dose.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Homo sapiens proteins
plain_language
Genetic defects can disable iodine recycling.
primary_references
[iodine-syn-iyd2008] Mutations in the iodotyrosine deiodinase gene and hypothyroidism. (2008). https://pubmed.ncbi.nlm.nih.gov/18434651/ DOI: 10.1056/nejmoa0706819
tissue_or_cell_type
In-vitro enzyme assays
trigger_kind
machinery_impairment Imported condition classification; unverified.
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 744–756
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Four selected patients from three unrelated families plus in-vitro mutant enzyme assays · source_derived_draft · unverified_draft
### iodine-syn-iyd-mutant-activity The IYD variants identified in four affected patients showed markedly reduced iodotyrosine-deiodinase activity in vitro. Condition category: machinery_impairment nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Genetic defects can disable iodine recycling. organism: Homo sapiens proteins tissue_or_cell_type: In-vitro enzyme assays experimental_model: Four selected patients from three unrelated families plus in-vitro mutant enzyme assays limitations: Abstract does not provide exact variant residues or assay dose. exposure: Two missense variants and one three-base-pair deletion; no nutrient-restriction experiment. cross_nutrient: true evidence_span: {"source_cache": "artifacts/iodine-synthesis-sources/18434651.json", "json_field": "abstractText", "text_sha256": "f257956854445e268691cd3df1388ca16cea3f41320a48753df200a381c56431", "text_characters": 914, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."} [iodine-syn-iyd2008] Mutations in the iodotyrosine deiodinase gene and hypothyroidism. (2008). https://pubmed.ncbi.nlm.nih.gov/18434651/ DOI: 10.1056/nejmoa0706819
Complete structured claim and evidence
The four patients with damaging IYD variants developed severe goitrous hypothyroidism evident in infancy or childhood.
Human IYD patient variant proteins studied in 2008 → Goitrous hypothyroidism source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
false
evidence_span
{"source_cache": "artifacts/iodine-synthesis-sources/18434651.json", "json_field": "abstractText", "text_sha256": "f257956854445e268691cd3df1388ca16cea3f41320a48753df200a381c56431", "text_characters": 914, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."}
experimental_model
Four selected patients from three unrelated families plus in-vitro mutant enzyme assays
exposure
Inherited enzyme variants in three unrelated families.
limitations
Selected cases; does not establish dietary deficiency or population prevalence.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Homo sapiens
plain_language
Failure to recycle iodine can impair hormone production after birth.
primary_references
[iodine-syn-iyd2008] Mutations in the iodotyrosine deiodinase gene and hypothyroidism. (2008). https://pubmed.ncbi.nlm.nih.gov/18434651/ DOI: 10.1056/nejmoa0706819
tissue_or_cell_type
Thyroid and systemic thyroid function
trigger_kind
machinery_impairment Imported condition classification; unverified.
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 758–770
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Four selected patients from three unrelated families plus in-vitro mutant enzyme assays · source_derived_draft · unverified_draft
### iodine-syn-iyd-mutant-phenotype The four patients with damaging IYD variants developed severe goitrous hypothyroidism evident in infancy or childhood. Condition category: machinery_impairment nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Failure to recycle iodine can impair hormone production after birth. organism: Homo sapiens tissue_or_cell_type: Thyroid and systemic thyroid function experimental_model: Four selected patients from three unrelated families plus in-vitro mutant enzyme assays limitations: Selected cases; does not establish dietary deficiency or population prevalence. exposure: Inherited enzyme variants in three unrelated families. cross_nutrient: false evidence_span: {"source_cache": "artifacts/iodine-synthesis-sources/18434651.json", "json_field": "abstractText", "text_sha256": "f257956854445e268691cd3df1388ca16cea3f41320a48753df200a381c56431", "text_characters": 914, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."} [iodine-syn-iyd2008] Mutations in the iodotyrosine deiodinase gene and hypothyroidism. (2008). https://pubmed.ncbi.nlm.nih.gov/18434651/ DOI: 10.1056/nejmoa0706819
Complete structured claim and evidence
Rats given 0.05% NaI in drinking water had lower thyroid NIS mRNA and protein at both 1 and 6 days.
Sodium iodide → Rat sodium/iodide symporter / Slc5a5 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
evidence_span
{"source_cache": "artifacts/iodine-synthesis-sources/10433193.json", "json_field": "abstractText", "text_sha256": "edf82df926d65731111d3f6b8005965a95e9928421170aa4cb5cef0709adc924", "text_characters": 2339, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."}
experimental_model
Rat oral and intraperitoneal sodium iodide experiments
exposure
0.05% sodium iodide in drinking water for 1 or 6 days.
limitations
Expression data support an escape mechanism but do not independently prove NIS reduction sufficient for escape.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Rattus norvegicus
plain_language
Sustained excess iodide reduced the thyroid uptake machinery in rats.
primary_references
[iodine-syn-escape1999] Escape from the acute Wolff-Chaikoff effect is associated with a decrease in thyroid sodium/iodide symporter messenger ribonucleic acid and protein. (1999). https://pubmed.ncbi.nlm.nih.gov/10433193/ DOI: 10.1210/endo.140.8.6893
tissue_or_cell_type
Thyroid
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 772–784
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat oral and intraperitoneal sodium iodide experiments · source_derived_draft · unverified_draft
### iodine-syn-escape-nis Rats given 0.05% NaI in drinking water had lower thyroid NIS mRNA and protein at both 1 and 6 days. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Sustained excess iodide reduced the thyroid uptake machinery in rats. organism: Rattus norvegicus tissue_or_cell_type: Thyroid experimental_model: Rat oral and intraperitoneal sodium iodide experiments limitations: Expression data support an escape mechanism but do not independently prove NIS reduction sufficient for escape. exposure: 0.05% sodium iodide in drinking water for 1 or 6 days. cross_nutrient: false evidence_span: {"source_cache": "artifacts/iodine-synthesis-sources/10433193.json", "json_field": "abstractText", "text_sha256": "edf82df926d65731111d3f6b8005965a95e9928421170aa4cb5cef0709adc924", "text_characters": 2339, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."} [iodine-syn-escape1999] Escape from the acute Wolff-Chaikoff effect is associated with a decrease in thyroid sodium/iodide symporter messenger ribonucleic acid and protein. (1999). https://pubmed.ncbi.nlm.nih.gov/10433193/ DOI: 10.1210/endo.140.8.6893
Complete structured claim and evidence
During continued 0.05% NaI exposure, rat serum T4 and T3 fell at day 1 but returned to normal by day 6.
Sodium iodide → Rat serum thyroid hormones source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
evidence_span
{"source_cache": "artifacts/iodine-synthesis-sources/10433193.json", "json_field": "abstractText", "text_sha256": "edf82df926d65731111d3f6b8005965a95e9928421170aa4cb5cef0709adc924", "text_characters": 2339, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."}
experimental_model
Rat oral and intraperitoneal sodium iodide experiments
exposure
0.05% sodium iodide in drinking water for 1 or 6 days.
limitations
Rodent pharmacological exposure; recovery time and susceptibility cannot be imposed on humans.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Rattus norvegicus
plain_language
The initial hormone suppression wore off despite continued high iodide exposure.
primary_references
[iodine-syn-escape1999] Escape from the acute Wolff-Chaikoff effect is associated with a decrease in thyroid sodium/iodide symporter messenger ribonucleic acid and protein. (1999). https://pubmed.ncbi.nlm.nih.gov/10433193/ DOI: 10.1210/endo.140.8.6893
tissue_or_cell_type
Serum
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 786–798
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat oral and intraperitoneal sodium iodide experiments · source_derived_draft · unverified_draft
### iodine-syn-escape-hormone-recovery During continued 0.05% NaI exposure, rat serum T4 and T3 fell at day 1 but returned to normal by day 6. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The initial hormone suppression wore off despite continued high iodide exposure. organism: Rattus norvegicus tissue_or_cell_type: Serum experimental_model: Rat oral and intraperitoneal sodium iodide experiments limitations: Rodent pharmacological exposure; recovery time and susceptibility cannot be imposed on humans. exposure: 0.05% sodium iodide in drinking water for 1 or 6 days. cross_nutrient: false evidence_span: {"source_cache": "artifacts/iodine-synthesis-sources/10433193.json", "json_field": "abstractText", "text_sha256": "edf82df926d65731111d3f6b8005965a95e9928421170aa4cb5cef0709adc924", "text_characters": 2339, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."} [iodine-syn-escape1999] Escape from the acute Wolff-Chaikoff effect is associated with a decrease in thyroid sodium/iodide symporter messenger ribonucleic acid and protein. (1999). https://pubmed.ncbi.nlm.nih.gov/10433193/ DOI: 10.1210/endo.140.8.6893
Complete structured claim and evidence
Iodide inhibited stimulated H2O2 generation in dog thyroid slices, including responses to probes acting downstream of receptor activation.
Iodide ion → Dog thyroid peroxide generation source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
evidence_span
{"source_cache": "artifacts/iodine-synthesis-sources/2841932.json", "json_field": "abstractText", "text_sha256": "00e19301656f8e8fdb9a047cfa29daf1c66f9a73c84d6c450ff805a6d8b497eb", "text_characters": 1113, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."}
experimental_model
Dog thyroid slices with iodide, stimulatory probes and methimazole
exposure
Iodide exposure in dog thyroid slices stimulated by thyrotropin, carbamylcholine or intracellular-signaling probes; concentrations not given in abstract.
limitations
Ex-vivo dog tissue; does not identify human DUOX2 as a directly bound molecular target.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Canis lupus familiaris
plain_language
Excess iodide can suppress the peroxide supply required for its own incorporation.
primary_references
[iodine-syn-block1988] Inhibition by iodide of iodide binding to proteins: the "Wolff-Chaikoff" effect is caused by inhibition of H2O2 generation. (1988). https://pubmed.ncbi.nlm.nih.gov/2841932/ DOI: 10.1016/0006-291x(88)90279-3
tissue_or_cell_type
Thyroid slices
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 800–812
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dog thyroid slices with iodide, stimulatory probes and methimazole · source_derived_draft · unverified_draft
### iodine-syn-acute-peroxide-block Iodide inhibited stimulated H2O2 generation in dog thyroid slices, including responses to probes acting downstream of receptor activation. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Excess iodide can suppress the peroxide supply required for its own incorporation. organism: Canis lupus familiaris tissue_or_cell_type: Thyroid slices experimental_model: Dog thyroid slices with iodide, stimulatory probes and methimazole limitations: Ex-vivo dog tissue; does not identify human DUOX2 as a directly bound molecular target. exposure: Iodide exposure in dog thyroid slices stimulated by thyrotropin, carbamylcholine or intracellular-signaling probes; concentrations not given in abstract. cross_nutrient: false evidence_span: {"source_cache": "artifacts/iodine-synthesis-sources/2841932.json", "json_field": "abstractText", "text_sha256": "00e19301656f8e8fdb9a047cfa29daf1c66f9a73c84d6c450ff805a6d8b497eb", "text_characters": 1113, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."} [iodine-syn-block1988] Inhibition by iodide of iodide binding to proteins: the "Wolff-Chaikoff" effect is caused by inhibition of H2O2 generation. (1988). https://pubmed.ncbi.nlm.nih.gov/2841932/ DOI: 10.1016/0006-291x(88)90279-3
Complete structured claim and evidence
Methimazole suppressed the inhibitory effects of iodide on stimulated H2O2 generation in dog thyroid slices.
Methimazole → Iodide induced peroxide inhibition source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
evidence_span
{"source_cache": "artifacts/iodine-synthesis-sources/2841932.json", "json_field": "abstractText", "text_sha256": "00e19301656f8e8fdb9a047cfa29daf1c66f9a73c84d6c450ff805a6d8b497eb", "text_characters": 1113, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."}
experimental_model
Dog thyroid slices with iodide, stimulatory probes and methimazole
exposure
Iodide exposure in dog thyroid slices stimulated by thyrotropin, carbamylcholine or intracellular-signaling probes; concentrations not given in abstract. Methimazole coexposure.
limitations
Pharmacological probe supports oxidation dependence; the inhibitory iodinated species was not identified.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Canis lupus familiaris
plain_language
Preventing iodide oxidation blocked this feedback effect in thyroid tissue.
primary_references
[iodine-syn-block1988] Inhibition by iodide of iodide binding to proteins: the "Wolff-Chaikoff" effect is caused by inhibition of H2O2 generation. (1988). https://pubmed.ncbi.nlm.nih.gov/2841932/ DOI: 10.1016/0006-291x(88)90279-3
tissue_or_cell_type
Thyroid slices
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 814–826
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dog thyroid slices with iodide, stimulatory probes and methimazole · source_derived_draft · unverified_draft
### iodine-syn-acute-block-oxidation Methimazole suppressed the inhibitory effects of iodide on stimulated H2O2 generation in dog thyroid slices. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Preventing iodide oxidation blocked this feedback effect in thyroid tissue. organism: Canis lupus familiaris tissue_or_cell_type: Thyroid slices experimental_model: Dog thyroid slices with iodide, stimulatory probes and methimazole limitations: Pharmacological probe supports oxidation dependence; the inhibitory iodinated species was not identified. exposure: Iodide exposure in dog thyroid slices stimulated by thyrotropin, carbamylcholine or intracellular-signaling probes; concentrations not given in abstract. Methimazole coexposure. cross_nutrient: false evidence_span: {"source_cache": "artifacts/iodine-synthesis-sources/2841932.json", "json_field": "abstractText", "text_sha256": "00e19301656f8e8fdb9a047cfa29daf1c66f9a73c84d6c450ff805a6d8b497eb", "text_characters": 1113, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."} [iodine-syn-block1988] Inhibition by iodide of iodide binding to proteins: the "Wolff-Chaikoff" effect is caused by inhibition of H2O2 generation. (1988). https://pubmed.ncbi.nlm.nih.gov/2841932/ DOI: 10.1016/0006-291x(88)90279-3
Complete structured claim and evidence
Purified hog TPO catalyzed iodine incorporation into hog thyroglobulin in kinetic assays of protein iodination.
Porcine thyroid peroxidase → Porcine thyroglobulin iodination source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
evidence_span
{"source_cache": "artifacts/iodine-synthesis-sources/6706940.json", "json_field": "abstractText", "text_sha256": "e7d184d64b66b0dc89f61c511688c79ffc9785b20233e7746ef4c97de351c78c", "text_characters": 1442, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."}
experimental_model
Purified hog thyroid peroxidase with hog thyroglobulin; steady-state and stopped-flow kinetics
exposure
Purified hog TPO; native TG with 1.0% iodine and further-iodinated TG with 1.2% iodine; reagent concentrations not stated in abstract.
limitations
Reaction measures TG iodination, not free iodotyrosine recycling. The proposed iodinium intermediate is a model, not imported as an established mechanism.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Sus scrofa
plain_language
TPO attaches iodine to tyrosine residues within the TG protein.
primary_references
[iodine-syn-tpo-iodination1984] Iodination and oxidation of thyroglobulin catalyzed by thyroid peroxidase. (1984). https://pubmed.ncbi.nlm.nih.gov/6706940/ DOI: 10.1016/s0021-9258(17)43667-2
tissue_or_cell_type
Purified thyroid enzyme and protein substrate
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 828–840
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified hog thyroid peroxidase with hog thyroglobulin; steady-state and stopped-flow kinetics · source_derived_draft · unverified_draft
### iodine-syn-tpo-protein-iodination Purified hog TPO catalyzed iodine incorporation into hog thyroglobulin in kinetic assays of protein iodination. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: TPO attaches iodine to tyrosine residues within the TG protein. organism: Sus scrofa tissue_or_cell_type: Purified thyroid enzyme and protein substrate experimental_model: Purified hog thyroid peroxidase with hog thyroglobulin; steady-state and stopped-flow kinetics limitations: Reaction measures TG iodination, not free iodotyrosine recycling. The proposed iodinium intermediate is a model, not imported as an established mechanism. exposure: Purified hog TPO; native TG with 1.0% iodine and further-iodinated TG with 1.2% iodine; reagent concentrations not stated in abstract. cross_nutrient: false evidence_span: {"source_cache": "artifacts/iodine-synthesis-sources/6706940.json", "json_field": "abstractText", "text_sha256": "e7d184d64b66b0dc89f61c511688c79ffc9785b20233e7746ef4c97de351c78c", "text_characters": 1442, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."} [iodine-syn-tpo-iodination1984] Iodination and oxidation of thyroglobulin catalyzed by thyroid peroxidase. (1984). https://pubmed.ncbi.nlm.nih.gov/6706940/ DOI: 10.1016/s0021-9258(17)43667-2
Complete structured claim and evidence
Recombinant human TPO catalyzed T4 formation from recombinant human TG in the direct TPO-versus-lactoperoxidase comparison.
Human TPO ectodomain residues 1–838 → Human thyroglobulin containing covalent T4 residues source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_span
{"source_cache": "artifacts/iodine-synthesis-sources/32025030.txt", "start_char": 37661, "end_char": 38631, "text_sha256": "edbab2cbd62ebd263ef59f543f10aad3692d3a3983ef5abad904e697ea34ca04", "text_characters": 970, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."}
experimental_model
Human TG cryo-EM, recombinant HEK293T-expressed TG and site-directed mutants
exposure
Extended Data Fig.6c: 0.1 micromolar TG, 1 mM KI, glucose/glucose oxidase peroxide supply, 10 minutes at 37 C; TPO added at fivefold the LPO concentration to compensate for approximately 20% heme occupancy; T4 measured after Pronase digestion.
limitations
This identifies the TPO-containing assay arm; most TG mutagenesis experiments used LPO. The measured T4 was liberated by assay proteolysis after formation on TG.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Homo sapiens TG and TPO; HEK293T TG expression and insect-cell TPO expression
plain_language
Human TPO can drive hormone formation on human thyroglobulin.
primary_references
[iodine-syn-tg2020] The structure of human thyroglobulin. (2020). https://pubmed.ncbi.nlm.nih.gov/32025030/ DOI: 10.1038/s41586-020-1995-4
tissue_or_cell_type
Purified-protein reconstitution
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 842–854
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human TG cryo-EM, recombinant HEK293T-expressed TG and site-directed mutants · source_derived_draft · unverified_draft
### iodine-syn-human-tpo-t4-synthesis Recombinant human TPO catalyzed T4 formation from recombinant human TG in the direct TPO-versus-lactoperoxidase comparison. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Human TPO can drive hormone formation on human thyroglobulin. organism: Homo sapiens TG and TPO; HEK293T TG expression and insect-cell TPO expression tissue_or_cell_type: Purified-protein reconstitution experimental_model: Human TG cryo-EM, recombinant HEK293T-expressed TG and site-directed mutants limitations: This identifies the TPO-containing assay arm; most TG mutagenesis experiments used LPO. The measured T4 was liberated by assay proteolysis after formation on TG. exposure: Extended Data Fig.6c: 0.1 micromolar TG, 1 mM KI, glucose/glucose oxidase peroxide supply, 10 minutes at 37 C; TPO added at fivefold the LPO concentration to compensate for approximately 20% heme occupancy; T4 measured after Pronase digestion. cross_nutrient: true evidence_span: {"source_cache": "artifacts/iodine-synthesis-sources/32025030.txt", "start_char": 37661, "end_char": 38631, "text_sha256": "edbab2cbd62ebd263ef59f543f10aad3692d3a3983ef5abad904e697ea34ca04", "text_characters": 970, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."} [iodine-syn-tg2020] The structure of human thyroglobulin. (2020). https://pubmed.ncbi.nlm.nih.gov/32025030/ DOI: 10.1038/s41586-020-1995-4
Complete structured claim and evidence
Iodinating human goiter TG with hog TPO for 90 minutes produced 0.3 T3 residues per TG molecule, measured after enzymatic hydrolysis.
Porcine thyroid peroxidase → Human thyroglobulin containing covalent T3 residues source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
evidence_span
{"source_cache": "artifacts/iodine-synthesis-sources/7372636.txt", "start_char": 6216, "end_char": 8536, "text_sha256": "753e684061b9063528196c840b23404015abc2b7b836a3887497aea0f8fe20a6", "text_characters": 2320, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."}
experimental_model
Purified hog TPO with human goiter TG or tyrosine-radiolabeled hog TG; chromatographic hormone and dehydroalanine analyses
exposure
Human goiter TG initially 0.04% iodine, iodinated for 90 minutes to approximately 60 iodine atoms per TG; the same preparation contained 2.6 T4 residues per molecule.
limitations
Reconstituted mixed-species experiment. Hormone residues are protein-bound before hydrolysis; the assay is not evidence that free MIT and DIT are routinely coupled in blood.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Sus scrofa enzyme; Homo sapiens substrate
plain_language
TPO-driven chemistry can make T3 directly within TG, before the hormone is released.
primary_references
[iodine-syn-tpo-coupling1980] Formation of dehydroalanine residues during thyroid hormone synthesis in thyroglobulin. (1980). https://pubmed.ncbi.nlm.nih.gov/7372636/ DOI: 10.1016/S0021-9258(19)70782-0
tissue_or_cell_type
Purified TPO and human goiter TG
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 856–868
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified hog TPO with human goiter TG or tyrosine-radiolabeled hog TG; chromatographic hormone and dehydroalanine analyses · source_derived_draft · unverified_draft
### iodine-syn-tpo-t3-formation Iodinating human goiter TG with hog TPO for 90 minutes produced 0.3 T3 residues per TG molecule, measured after enzymatic hydrolysis. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: TPO-driven chemistry can make T3 directly within TG, before the hormone is released. organism: Sus scrofa enzyme; Homo sapiens substrate tissue_or_cell_type: Purified TPO and human goiter TG experimental_model: Purified hog TPO with human goiter TG or tyrosine-radiolabeled hog TG; chromatographic hormone and dehydroalanine analyses limitations: Reconstituted mixed-species experiment. Hormone residues are protein-bound before hydrolysis; the assay is not evidence that free MIT and DIT are routinely coupled in blood. exposure: Human goiter TG initially 0.04% iodine, iodinated for 90 minutes to approximately 60 iodine atoms per TG; the same preparation contained 2.6 T4 residues per molecule. cross_nutrient: false evidence_span: {"source_cache": "artifacts/iodine-synthesis-sources/7372636.txt", "start_char": 6216, "end_char": 8536, "text_sha256": "753e684061b9063528196c840b23404015abc2b7b836a3887497aea0f8fe20a6", "text_characters": 2320, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."} [iodine-syn-tpo-coupling1980] Formation of dehydroalanine residues during thyroid hormone synthesis in thyroglobulin. (1980). https://pubmed.ncbi.nlm.nih.gov/7372636/ DOI: 10.1016/S0021-9258(19)70782-0
Complete structured claim and evidence
During TPO-catalyzed hormone formation in TG, approximately one protein-bound dehydroalanine residue was formed per hormone residue.
Porcine thyroid peroxidase → Thyroglobulin-bound dehydroalanyl residues source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
evidence_span
{"source_cache": "artifacts/iodine-synthesis-sources/7372636.txt", "start_char": 1081, "end_char": 2101, "text_sha256": "5ea5287db6f28391150ad5b783a0be5e450fd71f22b92028fefb7900c686c636", "text_characters": 1020, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."}
experimental_model
Purified hog TPO with human goiter TG or tyrosine-radiolabeled hog TG; chromatographic hormone and dehydroalanine analyses
exposure
Hog TPO with human goiter TG and radiolabeled hog TG; dehydroalanine quantified after benzyl-mercaptan addition or borohydride reduction and hydrolysis.
limitations
Chemical trapping identifies the retained donor remnant; it does not prove every proposed radical intermediate or identify individual T3 donor sites.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Sus scrofa enzyme; Homo sapiens and Sus scrofa TG in separate experiments
plain_language
Coupling leaves a dehydroalanine remnant on the donor side of TG while creating a hormone residue.
primary_references
[iodine-syn-tpo-coupling1980] Formation of dehydroalanine residues during thyroid hormone synthesis in thyroglobulin. (1980). https://pubmed.ncbi.nlm.nih.gov/7372636/ DOI: 10.1016/S0021-9258(19)70782-0
tissue_or_cell_type
Purified-protein reactions
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 870–882
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified hog TPO with human goiter TG or tyrosine-radiolabeled hog TG; chromatographic hormone and dehydroalanine analyses · source_derived_draft · unverified_draft
### iodine-syn-coupling-dehydroalanine During TPO-catalyzed hormone formation in TG, approximately one protein-bound dehydroalanine residue was formed per hormone residue. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Coupling leaves a dehydroalanine remnant on the donor side of TG while creating a hormone residue. organism: Sus scrofa enzyme; Homo sapiens and Sus scrofa TG in separate experiments tissue_or_cell_type: Purified-protein reactions experimental_model: Purified hog TPO with human goiter TG or tyrosine-radiolabeled hog TG; chromatographic hormone and dehydroalanine analyses limitations: Chemical trapping identifies the retained donor remnant; it does not prove every proposed radical intermediate or identify individual T3 donor sites. exposure: Hog TPO with human goiter TG and radiolabeled hog TG; dehydroalanine quantified after benzyl-mercaptan addition or borohydride reduction and hydrolysis. cross_nutrient: false evidence_span: {"source_cache": "artifacts/iodine-synthesis-sources/7372636.txt", "start_char": 1081, "end_char": 2101, "text_sha256": "5ea5287db6f28391150ad5b783a0be5e450fd71f22b92028fefb7900c686c636", "text_characters": 1020, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."} [iodine-syn-tpo-coupling1980] Formation of dehydroalanine residues during thyroid hormone synthesis in thyroglobulin. (1980). https://pubmed.ncbi.nlm.nih.gov/7372636/ DOI: 10.1016/S0021-9258(19)70782-0
Complete structured claim and evidence
Rat MCT8 expression increased uptake of 10 nM radiolabeled T4 approximately tenfold in Xenopus oocytes.
Rat MCT8 / Slc16a2 → Cellular thyroxine uptake source_derived_draftungraded
Experimental context and source evidence
evidence_locator
Primary abstract
evidence_spans
[{"source_document": "artifacts/iodine-metabolism-sources/12871948.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1490}]
experimental_model
Rat MCT8 cRNA expressed in Xenopus laevis oocytes
exposure
MCT8 cRNA; assay three days later with 10 nM 125I-labeled hormone; uptake linear for less than four minutes.
limitations
Rat transporter in an expression host; this is hormone transport, not intestinal iodide uptake.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Rat protein in Xenopus laevis
plain_language
MCT8 carries T4 across the cell membrane.
primary_references
[i-met-12871948] Identification of monocarboxylate transporter 8 as a specific thyroid hormone transporter. (2003). https://pubmed.ncbi.nlm.nih.gov/12871948/ DOI: 10.1074/jbc.m300909200
tissue_or_cell_type
Oocyte plasma membrane
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 884–896
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat MCT8 cRNA expressed in Xenopus laevis oocytes · source_derived_draft · unverified_draft
### i-met-rat-t4 Rat MCT8 expression increased uptake of 10 nM radiolabeled T4 approximately tenfold in Xenopus oocytes. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: MCT8 carries T4 across the cell membrane. organism: Rat protein in Xenopus laevis tissue_or_cell_type: Oocyte plasma membrane experimental_model: Rat MCT8 cRNA expressed in Xenopus laevis oocytes limitations: Rat transporter in an expression host; this is hormone transport, not intestinal iodide uptake. exposure: MCT8 cRNA; assay three days later with 10 nM 125I-labeled hormone; uptake linear for less than four minutes. evidence_locator: Primary abstract evidence_spans: [{"source_document": "artifacts/iodine-metabolism-sources/12871948.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1490}] [i-met-12871948] Identification of monocarboxylate transporter 8 as a specific thyroid hormone transporter. (2003). https://pubmed.ncbi.nlm.nih.gov/12871948/ DOI: 10.1074/jbc.m300909200
Complete structured claim and evidence
Rat MCT8 expression increased uptake of 10 nM radiolabeled T3 approximately tenfold in Xenopus oocytes.
Rat MCT8 / Slc16a2 → Cellular triiodothyronine uptake source_derived_draftungraded
Experimental context and source evidence
evidence_locator
Primary abstract
evidence_spans
[{"source_document": "artifacts/iodine-metabolism-sources/12871948.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1490}]
experimental_model
Rat MCT8 cRNA expressed in Xenopus laevis oocytes
exposure
MCT8 cRNA; assay three days later with 10 nM 125I-labeled hormone; uptake linear for less than four minutes.
limitations
Rat transporter in an expression host; this is hormone transport, not intestinal iodide uptake.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Rat protein in Xenopus laevis
plain_language
MCT8 carries T3 across the cell membrane.
primary_references
[i-met-12871948] Identification of monocarboxylate transporter 8 as a specific thyroid hormone transporter. (2003). https://pubmed.ncbi.nlm.nih.gov/12871948/ DOI: 10.1074/jbc.m300909200
tissue_or_cell_type
Oocyte plasma membrane
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 898–910
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat MCT8 cRNA expressed in Xenopus laevis oocytes · source_derived_draft · unverified_draft
### i-met-rat-t3 Rat MCT8 expression increased uptake of 10 nM radiolabeled T3 approximately tenfold in Xenopus oocytes. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: MCT8 carries T3 across the cell membrane. organism: Rat protein in Xenopus laevis tissue_or_cell_type: Oocyte plasma membrane experimental_model: Rat MCT8 cRNA expressed in Xenopus laevis oocytes limitations: Rat transporter in an expression host; this is hormone transport, not intestinal iodide uptake. exposure: MCT8 cRNA; assay three days later with 10 nM 125I-labeled hormone; uptake linear for less than four minutes. evidence_locator: Primary abstract evidence_spans: [{"source_document": "artifacts/iodine-metabolism-sources/12871948.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1490}] [i-met-12871948] Identification of monocarboxylate transporter 8 as a specific thyroid hormone transporter. (2003). https://pubmed.ncbi.nlm.nih.gov/12871948/ DOI: 10.1074/jbc.m300909200
Complete structured claim and evidence
Human MCT8 structure places the T3 carboxylate against Arg371 and its iodine atoms in hydrophobic pockets; substitutions of substrate-contact residues reduce cellular T3 uptake.
Human MCT8 / SLC16A2 → T3 source_derived_draftungraded
Experimental context and source evidence
evidence_locator
Results: T3 recognition, Figure 3; Methods
evidence_spans
[{"source_document": "artifacts/iodine-metabolism-sources/40140416.txt", "locator": "Results: T3 recognition, Figure 3; Methods", "start_char": 679, "end_char": 2779}]
experimental_model
Purified tagged human MCT8 from HEK293F cells; cryo-EM and cell-based mutagenesis
exposure
Cryo-EM preparation: 1.5 mM T3. HeLa uptake assay: human MCT8 and CRYM coexpression; 1 nM unlabeled T3 plus 0.02 microcuries 125I-T3 for 30 minutes at 37 C.
limitations
Purified structural occupancy is not a physiological concentration threshold. Individual mutations and their effects are not identical.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Human
plain_language
The transporter recognizes the shape and chemical groups of iodine-containing T3.
primary_references
[i-met-40140416] Structural insights into thyroid hormone transporter MCT8. (2025). https://pubmed.ncbi.nlm.nih.gov/40140416/ DOI: 10.1038/s41467-025-58131-8
tissue_or_cell_type
HeLa cells for transport; HEK293F cells for protein production
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 912–924
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified tagged human MCT8 from HEK293F cells; cryo-EM and cell-based mutagenesis · source_derived_draft · unverified_draft
### i-met-mct8-t3-recognition Human MCT8 structure places the T3 carboxylate against Arg371 and its iodine atoms in hydrophobic pockets; substitutions of substrate-contact residues reduce cellular T3 uptake. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The transporter recognizes the shape and chemical groups of iodine-containing T3. organism: Human tissue_or_cell_type: HeLa cells for transport; HEK293F cells for protein production experimental_model: Purified tagged human MCT8 from HEK293F cells; cryo-EM and cell-based mutagenesis limitations: Purified structural occupancy is not a physiological concentration threshold. Individual mutations and their effects are not identical. exposure: Cryo-EM preparation: 1.5 mM T3. HeLa uptake assay: human MCT8 and CRYM coexpression; 1 nM unlabeled T3 plus 0.02 microcuries 125I-T3 for 30 minutes at 37 C. evidence_locator: Results: T3 recognition, Figure 3; Methods evidence_spans: [{"source_document": "artifacts/iodine-metabolism-sources/40140416.txt", "locator": "Results: T3 recognition, Figure 3; Methods", "start_char": 679, "end_char": 2779}] [i-met-40140416] Structural insights into thyroid hormone transporter MCT8. (2025). https://pubmed.ncbi.nlm.nih.gov/40140416/ DOI: 10.1038/s41467-025-58131-8
Complete structured claim and evidence
Silychristin inhibited human MCT8-mediated T4 uptake in transfected HeLa cells; structural and binding experiments support trapping an outward-facing transporter state.
Silychristin → Cellular thyroxine uptake source_derived_draftungraded
Experimental context and source evidence
evidence_locator
Figures 1a-b and 4; Results: inhibitor mechanism
evidence_spans
[{"source_document": "artifacts/iodine-metabolism-sources/40368961.txt", "locator": "Figures 1a-b and 4; Results: inhibitor mechanism", "start_char": 17453, "end_char": 22253}]
experimental_model
Purified human MCT8 structures and microscale thermophoresis; transfected HeLa transport assays
exposure
Cell assays used 10 micromolar T4 with or without 10 micromolar silychristin.
limitations
Drug-compound experiment; does not establish dietary milk-thistle effects or an iodine-supplement interaction at usual exposure.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Human
plain_language
An experimental inhibitor can block hormone passage through MCT8.
primary_references
[i-met-40368961] Molecular mechanism of thyroxine transport by monocarboxylate transporters. (2025). https://pubmed.ncbi.nlm.nih.gov/40368961/ DOI: 10.1038/s41467-025-59751-w
tissue_or_cell_type
HeLa cells and purified MCT8
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 926–938
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human MCT8 structures and microscale thermophoresis; transfected HeLa transport assays · source_derived_draft · unverified_draft
### i-met-silychristin-mct8 Silychristin inhibited human MCT8-mediated T4 uptake in transfected HeLa cells; structural and binding experiments support trapping an outward-facing transporter state. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: An experimental inhibitor can block hormone passage through MCT8. organism: Human tissue_or_cell_type: HeLa cells and purified MCT8 experimental_model: Purified human MCT8 structures and microscale thermophoresis; transfected HeLa transport assays limitations: Drug-compound experiment; does not establish dietary milk-thistle effects or an iodine-supplement interaction at usual exposure. exposure: Cell assays used 10 micromolar T4 with or without 10 micromolar silychristin. evidence_locator: Figures 1a-b and 4; Results: inhibitor mechanism evidence_spans: [{"source_document": "artifacts/iodine-metabolism-sources/40368961.txt", "locator": "Figures 1a-b and 4; Results: inhibitor mechanism", "start_char": 17453, "end_char": 22253}] [i-met-40368961] Molecular mechanism of thyroxine transport by monocarboxylate transporters. (2025). https://pubmed.ncbi.nlm.nih.gov/40368961/ DOI: 10.1038/s41467-025-59751-w
Complete structured claim and evidence
Human MCT8 D424N retained measurable T4 binding but had strongly impaired cellular T4 transport, showing that binding alone does not establish transport competence.
Human MCT8 D424N (D498N in long isoform) → Cellular thyroxine uptake source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_locator
Figure 3; Figure 5 caption and Results: MCT8 pathogenic mutant
evidence_spans
[{"source_document": "artifacts/iodine-metabolism-sources/40368961.txt", "locator": "Figure 3; Figure 5 caption and Results: MCT8 pathogenic mutant", "start_char": 16912, "end_char": 18212}]
experimental_model
Purified human MCT8 structures and microscale thermophoresis; transfected HeLa transport assays
exposure
Patient-derived D424N short isoform, equivalent to D498N long isoform; wild-type comparator.
limitations
The proposed conformational explanation is structural interpretation; no dietary intervention.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Human
plain_language
A transporter may still bind hormone while failing to deliver it into cells.
primary_references
[i-met-40368961] Molecular mechanism of thyroxine transport by monocarboxylate transporters. (2025). https://pubmed.ncbi.nlm.nih.gov/40368961/ DOI: 10.1038/s41467-025-59751-w
tissue_or_cell_type
Purified mutant and HeLa cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 940–952
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human MCT8 structures and microscale thermophoresis; transfected HeLa transport assays · source_derived_draft · unverified_draft
### i-met-mct8-d424n-binding-transport Human MCT8 D424N retained measurable T4 binding but had strongly impaired cellular T4 transport, showing that binding alone does not establish transport competence. Condition category: machinery_impairment nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A transporter may still bind hormone while failing to deliver it into cells. organism: Human tissue_or_cell_type: Purified mutant and HeLa cells experimental_model: Purified human MCT8 structures and microscale thermophoresis; transfected HeLa transport assays limitations: The proposed conformational explanation is structural interpretation; no dietary intervention. exposure: Patient-derived D424N short isoform, equivalent to D498N long isoform; wild-type comparator. evidence_locator: Figure 3; Figure 5 caption and Results: MCT8 pathogenic mutant evidence_spans: [{"source_document": "artifacts/iodine-metabolism-sources/40368961.txt", "locator": "Figure 3; Figure 5 caption and Results: MCT8 pathogenic mutant", "start_char": 16912, "end_char": 18212}] [i-met-40368961] Molecular mechanism of thyroxine transport by monocarboxylate transporters. (2025). https://pubmed.ncbi.nlm.nih.gov/40368961/ DOI: 10.1038/s41467-025-59751-w
Complete structured claim and evidence
The 2.3-angstrom human OATP1C1 structure places T4 in a side pocket where K376, N399 and S562 coordinate the outer-ring hydroxyl group.
Human OATP1C1 / SLCO1C1 → T4 source_derived_draftungraded
Experimental context and source evidence
evidence_locator
Results: Structure and mechanism of T4 transport by OATP1C1; Figure 3
evidence_spans
[{"source_document": "artifacts/iodine-metabolism-sources/40680733.txt", "locator": "Results: Structure and mechanism of T4 transport by OATP1C1; Figure 3", "start_char": 30218, "end_char": 32418}]
experimental_model
Human OATP1C1 cryo-EM and stable HEK293 wild-type/mutant uptake assays
exposure
T4-bound cryo-EM structure; complementary radiolabeled-T4 uptake experiments.
limitations
Static structure; possible lateral entry and lipid cotransport are not established by this record.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Human
plain_language
OATP1C1 has a defined binding pocket for the thyroid hormone precursor T4.
primary_references
[i-met-40680733] Structural insights into brain thyroid hormone transport via MCT8 and OATP1C1. (2025). https://pubmed.ncbi.nlm.nih.gov/40680733/ DOI: 10.1016/j.cell.2025.06.032
tissue_or_cell_type
Purified human membrane transporter
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 954–966
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human OATP1C1 cryo-EM and stable HEK293 wild-type/mutant uptake assays · source_derived_draft · unverified_draft
### i-met-oatp1c1-t4-binding The 2.3-angstrom human OATP1C1 structure places T4 in a side pocket where K376, N399 and S562 coordinate the outer-ring hydroxyl group. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: OATP1C1 has a defined binding pocket for the thyroid hormone precursor T4. organism: Human tissue_or_cell_type: Purified human membrane transporter experimental_model: Human OATP1C1 cryo-EM and stable HEK293 wild-type/mutant uptake assays limitations: Static structure; possible lateral entry and lipid cotransport are not established by this record. exposure: T4-bound cryo-EM structure; complementary radiolabeled-T4 uptake experiments. evidence_locator: Results: Structure and mechanism of T4 transport by OATP1C1; Figure 3 evidence_spans: [{"source_document": "artifacts/iodine-metabolism-sources/40680733.txt", "locator": "Results: Structure and mechanism of T4 transport by OATP1C1; Figure 3", "start_char": 30218, "end_char": 32418}] [i-met-40680733] Structural insights into brain thyroid hormone transport via MCT8 and OATP1C1. (2025). https://pubmed.ncbi.nlm.nih.gov/40680733/ DOI: 10.1016/j.cell.2025.06.032
Complete structured claim and evidence
Human OATP1C1 K376A abolished measured radiolabeled-T4 uptake without lowering cell-surface expression relative to wild type.
Human OATP1C1 K376A → Cellular thyroxine uptake source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_locator
Figure 3E and Supplemental Figure S3B
evidence_spans
[{"source_document": "artifacts/iodine-metabolism-sources/40680733.txt", "locator": "Figure 3E and Supplemental Figure S3B", "start_char": 30544, "end_char": 32244}]
experimental_model
Human OATP1C1 cryo-EM and stable HEK293 wild-type/mutant uptake assays
exposure
K376A versus wild type; 0.5 nM 125I-T4 for 30 minutes at 37 C in DMEM with 0.1% BSA; three independent uptake experiments.
limitations
Engineered alanine mutant; no in-vivo dose or dietary threshold inferred.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Human
plain_language
This pocket residue affects transport function even when the carrier reaches the membrane.
primary_references
[i-met-40680733] Structural insights into brain thyroid hormone transport via MCT8 and OATP1C1. (2025). https://pubmed.ncbi.nlm.nih.gov/40680733/ DOI: 10.1016/j.cell.2025.06.032
tissue_or_cell_type
Stable HEK293 cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 968–980
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human OATP1C1 cryo-EM and stable HEK293 wild-type/mutant uptake assays · source_derived_draft · unverified_draft
### i-met-oatp-k376a Human OATP1C1 K376A abolished measured radiolabeled-T4 uptake without lowering cell-surface expression relative to wild type. Condition category: machinery_impairment nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: This pocket residue affects transport function even when the carrier reaches the membrane. organism: Human tissue_or_cell_type: Stable HEK293 cells experimental_model: Human OATP1C1 cryo-EM and stable HEK293 wild-type/mutant uptake assays limitations: Engineered alanine mutant; no in-vivo dose or dietary threshold inferred. exposure: K376A versus wild type; 0.5 nM 125I-T4 for 30 minutes at 37 C in DMEM with 0.1% BSA; three independent uptake experiments. evidence_locator: Figure 3E and Supplemental Figure S3B evidence_spans: [{"source_document": "artifacts/iodine-metabolism-sources/40680733.txt", "locator": "Figure 3E and Supplemental Figure S3B", "start_char": 30544, "end_char": 32244}] [i-met-40680733] Structural insights into brain thyroid hormone transport via MCT8 and OATP1C1. (2025). https://pubmed.ncbi.nlm.nih.gov/40680733/ DOI: 10.1016/j.cell.2025.06.032
Complete structured claim and evidence
Brain uptake of injected radiolabeled T4 was strongly reduced in Mct8/Oatp1c1 double-knockout mice; either single knockout retained roughly half the wild-type uptake.
Mouse Mct8/Oatp1c1 double knockout → Thyroxine entry into brain source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_locator
Figure 3A and Results: In vivo T4 transport studies
evidence_spans
[{"source_document": "artifacts/iodine-metabolism-sources/24691440.txt", "locator": "Figure 3A and Results: In vivo T4 transport studies", "start_char": 23660, "end_char": 25360}]
experimental_model
Global Mct8 and Oatp1c1 single/double knockout mice, adult tracer experiments and P21 tissue assays
exposure
Adults received 1.2 microcuries 125I-T4 intraperitoneally; n=3 per genotype and time point.
limitations
Tracer accumulation is a transport measurement; murine redundancy is not proof of equivalent human compensation.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Mus musculus
plain_language
The two mouse transporters provide partly overlapping routes into the brain.
primary_references
[i-met-24691440] Transporters MCT8 and OATP1C1 maintain murine brain thyroid hormone homeostasis. (2014). https://pubmed.ncbi.nlm.nih.gov/24691440/ DOI: 10.1172/jci70324
tissue_or_cell_type
Brain after systemic tracer injection
trigger_kind
machinery_impairment Imported condition classification; unverified.
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 982–994
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Global Mct8 and Oatp1c1 single/double knockout mice, adult tracer experiments and P21 tissue assays · source_derived_draft · unverified_draft
### i-met-double-ko-t4-entry Brain uptake of injected radiolabeled T4 was strongly reduced in Mct8/Oatp1c1 double-knockout mice; either single knockout retained roughly half the wild-type uptake. Condition category: machinery_impairment nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The two mouse transporters provide partly overlapping routes into the brain. organism: Mus musculus tissue_or_cell_type: Brain after systemic tracer injection experimental_model: Global Mct8 and Oatp1c1 single/double knockout mice, adult tracer experiments and P21 tissue assays limitations: Tracer accumulation is a transport measurement; murine redundancy is not proof of equivalent human compensation. exposure: Adults received 1.2 microcuries 125I-T4 intraperitoneally; n=3 per genotype and time point. evidence_locator: Figure 3A and Results: In vivo T4 transport studies evidence_spans: [{"source_document": "artifacts/iodine-metabolism-sources/24691440.txt", "locator": "Figure 3A and Results: In vivo T4 transport studies", "start_char": 23660, "end_char": 25360}] [i-met-24691440] Transporters MCT8 and OATP1C1 maintain murine brain thyroid hormone homeostasis. (2014). https://pubmed.ncbi.nlm.nih.gov/24691440/ DOI: 10.1172/jci70324
Complete structured claim and evidence
At postnatal day 21, double-knockout forebrain T3 content was approximately 10% of wild type, whereas Oatp1c1 single-knockout forebrain T3 was preserved.
Mouse Mct8/Oatp1c1 double knockout → Brain triiodothyronine content source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_locator
Figure 3B and Results: Analysis of TH content and metabolism in the brain
evidence_spans
[{"source_document": "artifacts/iodine-metabolism-sources/24691440.txt", "locator": "Figure 3B and Results: Analysis of TH content and metabolism in the brain", "start_char": 26251, "end_char": 27951}]
experimental_model
Global Mct8 and Oatp1c1 single/double knockout mice, adult tracer experiments and P21 tissue assays
exposure
P21, n=8 per genotype; hormone content measurements.
limitations
The content result is local to mouse forebrain and this developmental time.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Mus musculus
plain_language
Losing both transport routes overwhelms the compensation seen after one loss.
primary_references
[i-met-24691440] Transporters MCT8 and OATP1C1 maintain murine brain thyroid hormone homeostasis. (2014). https://pubmed.ncbi.nlm.nih.gov/24691440/ DOI: 10.1172/jci70324
tissue_or_cell_type
Perfused forebrain
trigger_kind
machinery_impairment Imported condition classification; unverified.
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 996–1008
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Global Mct8 and Oatp1c1 single/double knockout mice, adult tracer experiments and P21 tissue assays · source_derived_draft · unverified_draft
### i-met-double-ko-brain-t3 At postnatal day 21, double-knockout forebrain T3 content was approximately 10% of wild type, whereas Oatp1c1 single-knockout forebrain T3 was preserved. Condition category: machinery_impairment nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Losing both transport routes overwhelms the compensation seen after one loss. organism: Mus musculus tissue_or_cell_type: Perfused forebrain experimental_model: Global Mct8 and Oatp1c1 single/double knockout mice, adult tracer experiments and P21 tissue assays limitations: The content result is local to mouse forebrain and this developmental time. exposure: P21, n=8 per genotype; hormone content measurements. evidence_locator: Figure 3B and Results: Analysis of TH content and metabolism in the brain evidence_spans: [{"source_document": "artifacts/iodine-metabolism-sources/24691440.txt", "locator": "Figure 3B and Results: Analysis of TH content and metabolism in the brain", "start_char": 26251, "end_char": 27951}] [i-met-24691440] Transporters MCT8 and OATP1C1 maintain murine brain thyroid hormone homeostasis. (2014). https://pubmed.ncbi.nlm.nih.gov/24691440/ DOI: 10.1172/jci70324
Complete structured claim and evidence
D2 activity in P21 forebrain and cerebellum rose almost tenfold in Mct8/Oatp1c1 double-knockout mice despite persistent severe brain hormone depletion.
Mouse Mct8/Oatp1c1 double knockout → Mouse type 2 iodothyronine deiodinase source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Selenium-containing D2 processes iodine-containing T4; genetic transport failure persists despite increased enzyme activity.
evidence_locator
Figure 4A and Results: Analysis of TH content and metabolism in the brain
evidence_spans
[{"source_document": "artifacts/iodine-metabolism-sources/24691440.txt", "locator": "Figure 4A and Results: Analysis of TH content and metabolism in the brain", "start_char": 26902, "end_char": 28402}]
experimental_model
Global Mct8 and Oatp1c1 single/double knockout mice, adult tracer experiments and P21 tissue assays
exposure
P21 double knockout versus wild type; D2 activity assay.
limitations
This is compensatory enzyme activity, not demonstration that selenium supplementation repairs transporter loss.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Mus musculus
plain_language
The brain increases local hormone activation machinery, but this cannot replace missing substrate delivery.
primary_references
[i-met-24691440] Transporters MCT8 and OATP1C1 maintain murine brain thyroid hormone homeostasis. (2014). https://pubmed.ncbi.nlm.nih.gov/24691440/ DOI: 10.1172/jci70324
tissue_or_cell_type
Forebrain and cerebellum homogenates
trigger_kind
machinery_impairment Imported condition classification; unverified.
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 1010–1023
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Global Mct8 and Oatp1c1 single/double knockout mice, adult tracer experiments and P21 tissue assays · source_derived_draft · unverified_draft
### i-met-double-ko-dio2-response D2 activity in P21 forebrain and cerebellum rose almost tenfold in Mct8/Oatp1c1 double-knockout mice despite persistent severe brain hormone depletion. Condition category: machinery_impairment nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The brain increases local hormone activation machinery, but this cannot replace missing substrate delivery. organism: Mus musculus tissue_or_cell_type: Forebrain and cerebellum homogenates experimental_model: Global Mct8 and Oatp1c1 single/double knockout mice, adult tracer experiments and P21 tissue assays limitations: This is compensatory enzyme activity, not demonstration that selenium supplementation repairs transporter loss. exposure: P21 double knockout versus wild type; D2 activity assay. cross_nutrient: Selenium-containing D2 processes iodine-containing T4; genetic transport failure persists despite increased enzyme activity. evidence_locator: Figure 4A and Results: Analysis of TH content and metabolism in the brain evidence_spans: [{"source_document": "artifacts/iodine-metabolism-sources/24691440.txt", "locator": "Figure 4A and Results: Analysis of TH content and metabolism in the brain", "start_char": 26902, "end_char": 28402}] [i-met-24691440] Transporters MCT8 and OATP1C1 maintain murine brain thyroid hormone homeostasis. (2014). https://pubmed.ncbi.nlm.nih.gov/24691440/ DOI: 10.1172/jci70324
Complete structured claim and evidence
T4 suppressed serum TSH in hypothyroid wild-type mice but not Dio2-null mice; administered T3 suppressed TSH in both genotypes.
Mouse Dio2 knockout → Serum TSH concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Selenoenzyme D2 activates an iodine-containing hormone for feedback; knockout is a machinery experiment.
evidence_locator
Results: TSH Suppression Studies and Figure 9; pages 2140–2141.
evidence_spans
[{"source_document": "artifacts/iodine-metabolism-sources/11731615.txt", "locator": "Primary article Results, Figures 7 and 9; Methods: Assays for Serum T4, T3 and TSH, page 2146", "start_char": 20490, "end_char": 22790}]
experimental_model
Dio2-null mice and wild-type littermates, including hormone challenge after hypothyroidism
exposure
Male mice made hypothyroid for four weeks with methimazole/perchlorate; PTU inhibited D1. Subcutaneous T4 3 micrograms/100 g body weight or T3 1.2 micrograms/100 g; serum collected five hours later.
limitations
Pharmacologic hormone challenge after thyroid synthesis blockade and D1 inhibition; not a human dosing rule or dietary selenium-deficiency experiment.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Mus musculus
plain_language
T3 bypassed the missing local T4-activation step in this feedback experiment.
primary_references
[i-met-11731615] Targeted disruption of the type 2 selenodeiodinase gene (DIO2) results in a phenotype of pituitary resistance to T4. (2001). https://pubmed.ncbi.nlm.nih.gov/11731615/ DOI: 10.1210/mend.15.12.0740
tissue_or_cell_type
Pituitary feedback and serum TSH
trigger_kind
machinery_impairment Imported condition classification; unverified.
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 1025–1038
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dio2-null mice and wild-type littermates, including hormone challenge after hypothyroidism · source_derived_draft · unverified_draft
### i-met-dio2-t4-feedback T4 suppressed serum TSH in hypothyroid wild-type mice but not Dio2-null mice; administered T3 suppressed TSH in both genotypes. Condition category: machinery_impairment nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: T3 bypassed the missing local T4-activation step in this feedback experiment. organism: Mus musculus tissue_or_cell_type: Pituitary feedback and serum TSH experimental_model: Dio2-null mice and wild-type littermates, including hormone challenge after hypothyroidism limitations: Pharmacologic hormone challenge after thyroid synthesis blockade and D1 inhibition; not a human dosing rule or dietary selenium-deficiency experiment. exposure: Male mice made hypothyroid for four weeks with methimazole/perchlorate; PTU inhibited D1. Subcutaneous T4 3 micrograms/100 g body weight or T3 1.2 micrograms/100 g; serum collected five hours later. cross_nutrient: Selenoenzyme D2 activates an iodine-containing hormone for feedback; knockout is a machinery experiment. evidence_locator: Results: TSH Suppression Studies and Figure 9; pages 2140–2141. evidence_spans: [{"source_document": "artifacts/iodine-metabolism-sources/11731615.txt", "locator": "Primary article Results, Figures 7 and 9; Methods: Assays for Serum T4, T3 and TSH, page 2146", "start_char": 20490, "end_char": 22790}] [i-met-11731615] Targeted disruption of the type 2 selenodeiodinase gene (DIO2) results in a phenotype of pituitary resistance to T4. (2001). https://pubmed.ncbi.nlm.nih.gov/11731615/ DOI: 10.1210/mend.15.12.0740
Complete structured claim and evidence
Adult Dio2-null mice had serum total T3 comparable to wild type despite complete loss of measured D2 activity and elevated serum T4 and TSH.
Mouse Dio2 knockout → Serum total triiodothyronine concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_locator
Results: serum hormone levels, Figure 7; Methods page 2146: Assays for Serum T4, T3 and TSH.
evidence_spans
[{"source_document": "artifacts/iodine-metabolism-sources/11731615.txt", "locator": "Primary article Results, Figures 7 and 9; Methods: Assays for Serum T4, T3 and TSH, page 2146", "start_char": 17896, "end_char": 18546}, {"source_document": "artifacts/iodine-metabolism-sources/11731615.txt", "locator": "Methods page 2146, total-T3 assay identity and mouse-serum correction", "start_char": 29655, "end_char": 31355}]
experimental_model
Dio2-null mice and wild-type littermates, including hormone challenge after hypothyroidism
exposure
Adult mice aged 10–12 weeks; total-T3 Coat-A-Count radioimmunoassay with correction for a nonspecific mouse-serum effect.
limitations
Specific mouse compensation; not a diagnostic rule for hidden tissue hypothyroidism in humans.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Mus musculus
plain_language
A normal circulating T3 result did not mean that the deleted enzyme was functioning.
primary_references
[i-met-11731615] Targeted disruption of the type 2 selenodeiodinase gene (DIO2) results in a phenotype of pituitary resistance to T4. (2001). https://pubmed.ncbi.nlm.nih.gov/11731615/ DOI: 10.1210/mend.15.12.0740
tissue_or_cell_type
Serum and surveyed tissues
trigger_kind
machinery_impairment Imported condition classification; unverified.
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 1040–1052
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dio2-null mice and wild-type littermates, including hormone challenge after hypothyroidism · source_derived_draft · unverified_draft
### i-met-dio2-ko-serum-t3 Adult Dio2-null mice had serum total T3 comparable to wild type despite complete loss of measured D2 activity and elevated serum T4 and TSH. Condition category: machinery_impairment nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A normal circulating T3 result did not mean that the deleted enzyme was functioning. organism: Mus musculus tissue_or_cell_type: Serum and surveyed tissues experimental_model: Dio2-null mice and wild-type littermates, including hormone challenge after hypothyroidism limitations: Specific mouse compensation; not a diagnostic rule for hidden tissue hypothyroidism in humans. exposure: Adult mice aged 10–12 weeks; total-T3 Coat-A-Count radioimmunoassay with correction for a nonspecific mouse-serum effect. evidence_locator: Results: serum hormone levels, Figure 7; Methods page 2146: Assays for Serum T4, T3 and TSH. evidence_spans: [{"source_document": "artifacts/iodine-metabolism-sources/11731615.txt", "locator": "Primary article Results, Figures 7 and 9; Methods: Assays for Serum T4, T3 and TSH, page 2146", "start_char": 17896, "end_char": 18546}, {"source_document": "artifacts/iodine-metabolism-sources/11731615.txt", "locator": "Methods page 2146, total-T3 assay identity and mouse-serum correction", "start_char": 29655, "end_char": 31355}] [i-met-11731615] Targeted disruption of the type 2 selenodeiodinase gene (DIO2) results in a phenotype of pituitary resistance to T4. (2001). https://pubmed.ncbi.nlm.nih.gov/11731615/ DOI: 10.1210/mend.15.12.0740
Complete structured claim and evidence
Selenium-restricted rats had lower hepatic type I deiodinase activity than selenium-supplemented groups after 20 weeks.
Selenium → Rat type 1 iodothyronine deiodinase source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Selenium supply changes processing/defense associated with iodine-containing thyroid hormones; effects differ by tissue and enzyme.
evidence_locator
Primary abstract
evidence_spans
[{"source_document": "artifacts/iodine-metabolism-sources/8505673.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1565}]
experimental_model
Male weanling Sprague-Dawley rats fed torula-yeast diets for 20 weeks
exposure
20 weeks; basal 0.01 mg Se/kg diet versus basal diet plus sodium selenite reported at 0.05, 0.1 or 0.5 mg Se/kg diet.
limitations
Rat feeding study; no universal serum selenium threshold or human repletion dose. Glutathione peroxidase assay does not identify a specific isoform.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Rattus norvegicus
plain_language
Limited selenium supply reduced liver hormone-processing activity.
primary_references
[i-met-8505673] Selenium requirements of rats for normal hepatic and thyroidal 5'-deiodinase (type I) activities. (1993). https://pubmed.ncbi.nlm.nih.gov/8505673/ DOI: 10.1093/jn/123.6.1124
tissue_or_cell_type
Liver
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 1054–1067
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Male weanling Sprague-Dawley rats fed torula-yeast diets for 20 weeks · source_derived_draft · unverified_draft
### i-met-se-liver-dio1 Selenium-restricted rats had lower hepatic type I deiodinase activity than selenium-supplemented groups after 20 weeks. Condition category: nutrient_deficiency nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Limited selenium supply reduced liver hormone-processing activity. organism: Rattus norvegicus tissue_or_cell_type: Liver experimental_model: Male weanling Sprague-Dawley rats fed torula-yeast diets for 20 weeks limitations: Rat feeding study; no universal serum selenium threshold or human repletion dose. Glutathione peroxidase assay does not identify a specific isoform. exposure: 20 weeks; basal 0.01 mg Se/kg diet versus basal diet plus sodium selenite reported at 0.05, 0.1 or 0.5 mg Se/kg diet. cross_nutrient: Selenium supply changes processing/defense associated with iodine-containing thyroid hormones; effects differ by tissue and enzyme. evidence_locator: Primary abstract evidence_spans: [{"source_document": "artifacts/iodine-metabolism-sources/8505673.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1565}] [i-met-8505673] Selenium requirements of rats for normal hepatic and thyroidal 5'-deiodinase (type I) activities. (1993). https://pubmed.ncbi.nlm.nih.gov/8505673/ DOI: 10.1093/jn/123.6.1124
Complete structured claim and evidence
The same 20-week selenium-restricted diet did not suppress thyroid type I deiodinase activity, despite depressed liver activity.
Selenium → Rat type 1 iodothyronine deiodinase source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Selenium supply changes processing/defense associated with iodine-containing thyroid hormones; effects differ by tissue and enzyme.
evidence_locator
Primary abstract
evidence_spans
[{"source_document": "artifacts/iodine-metabolism-sources/8505673.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1565}]
experimental_model
Male weanling Sprague-Dawley rats fed torula-yeast diets for 20 weeks
exposure
20 weeks; basal 0.01 mg Se/kg diet versus basal diet plus sodium selenite reported at 0.05, 0.1 or 0.5 mg Se/kg diet.
limitations
Rat feeding study; no universal serum selenium threshold or human repletion dose. Glutathione peroxidase assay does not identify a specific isoform.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Rattus norvegicus
plain_language
The thyroid preserved this enzyme under conditions that impaired the liver.
primary_references
[i-met-8505673] Selenium requirements of rats for normal hepatic and thyroidal 5'-deiodinase (type I) activities. (1993). https://pubmed.ncbi.nlm.nih.gov/8505673/ DOI: 10.1093/jn/123.6.1124
tissue_or_cell_type
Thyroid
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 1069–1082
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Male weanling Sprague-Dawley rats fed torula-yeast diets for 20 weeks · source_derived_draft · unverified_draft
### i-met-se-thyroid-dio1 The same 20-week selenium-restricted diet did not suppress thyroid type I deiodinase activity, despite depressed liver activity. Condition category: nutrient_deficiency nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The thyroid preserved this enzyme under conditions that impaired the liver. organism: Rattus norvegicus tissue_or_cell_type: Thyroid experimental_model: Male weanling Sprague-Dawley rats fed torula-yeast diets for 20 weeks limitations: Rat feeding study; no universal serum selenium threshold or human repletion dose. Glutathione peroxidase assay does not identify a specific isoform. exposure: 20 weeks; basal 0.01 mg Se/kg diet versus basal diet plus sodium selenite reported at 0.05, 0.1 or 0.5 mg Se/kg diet. cross_nutrient: Selenium supply changes processing/defense associated with iodine-containing thyroid hormones; effects differ by tissue and enzyme. evidence_locator: Primary abstract evidence_spans: [{"source_document": "artifacts/iodine-metabolism-sources/8505673.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1565}] [i-met-8505673] Selenium requirements of rats for normal hepatic and thyroidal 5'-deiodinase (type I) activities. (1993). https://pubmed.ncbi.nlm.nih.gov/8505673/ DOI: 10.1093/jn/123.6.1124
Complete structured claim and evidence
Thyroid glutathione peroxidase activity in selenium-restricted rats was approximately 40% of that in supplemented groups although thyroid type I deiodinase was maintained.
Selenium → Rat thyroid glutathione peroxidase activity source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Selenium supply changes processing/defense associated with iodine-containing thyroid hormones; effects differ by tissue and enzyme.
evidence_locator
Primary abstract
evidence_spans
[{"source_document": "artifacts/iodine-metabolism-sources/8505673.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1565}]
experimental_model
Male weanling Sprague-Dawley rats fed torula-yeast diets for 20 weeks
exposure
20 weeks; basal 0.01 mg Se/kg diet versus basal diet plus sodium selenite reported at 0.05, 0.1 or 0.5 mg Se/kg diet.
limitations
Rat feeding study; no universal serum selenium threshold or human repletion dose. Glutathione peroxidase assay does not identify a specific isoform.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Rattus norvegicus
plain_language
Selenium restriction affected thyroid antioxidant activity differently from thyroid deiodination.
primary_references
[i-met-8505673] Selenium requirements of rats for normal hepatic and thyroidal 5'-deiodinase (type I) activities. (1993). https://pubmed.ncbi.nlm.nih.gov/8505673/ DOI: 10.1093/jn/123.6.1124
tissue_or_cell_type
Thyroid
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 1084–1097
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Male weanling Sprague-Dawley rats fed torula-yeast diets for 20 weeks · source_derived_draft · unverified_draft
### i-met-se-thyroid-gpx Thyroid glutathione peroxidase activity in selenium-restricted rats was approximately 40% of that in supplemented groups although thyroid type I deiodinase was maintained. Condition category: nutrient_deficiency nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Selenium restriction affected thyroid antioxidant activity differently from thyroid deiodination. organism: Rattus norvegicus tissue_or_cell_type: Thyroid experimental_model: Male weanling Sprague-Dawley rats fed torula-yeast diets for 20 weeks limitations: Rat feeding study; no universal serum selenium threshold or human repletion dose. Glutathione peroxidase assay does not identify a specific isoform. exposure: 20 weeks; basal 0.01 mg Se/kg diet versus basal diet plus sodium selenite reported at 0.05, 0.1 or 0.5 mg Se/kg diet. cross_nutrient: Selenium supply changes processing/defense associated with iodine-containing thyroid hormones; effects differ by tissue and enzyme. evidence_locator: Primary abstract evidence_spans: [{"source_document": "artifacts/iodine-metabolism-sources/8505673.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1565}] [i-met-8505673] Selenium requirements of rats for normal hepatic and thyroidal 5'-deiodinase (type I) activities. (1993). https://pubmed.ncbi.nlm.nih.gov/8505673/ DOI: 10.1093/jn/123.6.1124
Complete structured claim and evidence
Fibroblasts from affected siblings with a recessive SECISBP2 defect had reduced DIO2 activity; linkage did not map the defect to DIO2 itself.
Patients with recessive SECISBP2 defects → DIO2 source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Selenium-incorporation machinery is required for hormone-processing selenoproteins; this is not dietary selenium deficiency.
evidence_locator
Primary abstract
evidence_spans
[{"source_document": "artifacts/iodine-metabolism-sources/16228000.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1084}]
experimental_model
Two human families with recessive SECISBP2 variants; patient fibroblast enzyme assays and linkage analysis
exposure
Inherited SECISBP2 variants; no dietary deprivation exposure.
limitations
Abstract-only; variant-specific kinetics and dietary rescue were not established.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Homo sapiens
plain_language
A defect in selenium-incorporation machinery can impair thyroid-hormone processing even when the deiodinase gene is not the cause.
primary_references
[i-met-16228000] Mutations in SECISBP2 result in abnormal thyroid hormone metabolism. (2005). https://pubmed.ncbi.nlm.nih.gov/16228000/ DOI: 10.1038/ng1654
tissue_or_cell_type
Patient fibroblasts
trigger_kind
machinery_impairment Imported condition classification; unverified.
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 1099–1112
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two human families with recessive SECISBP2 variants; patient fibroblast enzyme assays and linkage analysis · source_derived_draft · unverified_draft
### i-met-secisbp2-fibroblast-dio2 Fibroblasts from affected siblings with a recessive SECISBP2 defect had reduced DIO2 activity; linkage did not map the defect to DIO2 itself. Condition category: machinery_impairment nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A defect in selenium-incorporation machinery can impair thyroid-hormone processing even when the deiodinase gene is not the cause. organism: Homo sapiens tissue_or_cell_type: Patient fibroblasts experimental_model: Two human families with recessive SECISBP2 variants; patient fibroblast enzyme assays and linkage analysis limitations: Abstract-only; variant-specific kinetics and dietary rescue were not established. exposure: Inherited SECISBP2 variants; no dietary deprivation exposure. cross_nutrient: Selenium-incorporation machinery is required for hormone-processing selenoproteins; this is not dietary selenium deficiency. evidence_locator: Primary abstract evidence_spans: [{"source_document": "artifacts/iodine-metabolism-sources/16228000.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1084}] [i-met-16228000] Mutations in SECISBP2 result in abnormal thyroid hormone metabolism. (2005). https://pubmed.ncbi.nlm.nih.gov/16228000/ DOI: 10.1038/ng1654
Complete structured claim and evidence
Cloning and characterization of human DIO2 cDNA identified DIO2 as a selenoprotein.
DIO2 → Protein-incorporated selenocysteine residue source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Selenium-containing DIO2 metabolizes iodine-containing T4.
evidence_locator
Primary abstract
evidence_spans
[{"source_document": "artifacts/iodine-metabolism-sources/8755651.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1406}]
experimental_model
Rat and human DIO2 cDNA cloning and characterization
exposure
DIO2 sequence and functional characterization; no nutritional intervention.
limitations
Protein composition does not establish a dietary threshold, benefit from extra selenium, or species-independent regulation.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Human DIO2; study also characterized rat orthologue
plain_language
The T4-activating enzyme contains selenium as part of its protein structure.
primary_references
[i-met-8755651] Cloning of the mammalian type II iodothyronine deiodinase. A selenoprotein differentially expressed and regulated in human and rat brain and other tissues. (1996). https://pubmed.ncbi.nlm.nih.gov/8755651/ DOI: 10.1172/jci118806
tissue_or_cell_type
Human cDNA and expression characterization
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 1114–1127
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat and human DIO2 cDNA cloning and characterization · source_derived_draft · unverified_draft
### i-met-human-dio2-selenoprotein Cloning and characterization of human DIO2 cDNA identified DIO2 as a selenoprotein. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The T4-activating enzyme contains selenium as part of its protein structure. organism: Human DIO2; study also characterized rat orthologue tissue_or_cell_type: Human cDNA and expression characterization experimental_model: Rat and human DIO2 cDNA cloning and characterization limitations: Protein composition does not establish a dietary threshold, benefit from extra selenium, or species-independent regulation. exposure: DIO2 sequence and functional characterization; no nutritional intervention. cross_nutrient: Selenium-containing DIO2 metabolizes iodine-containing T4. evidence_locator: Primary abstract evidence_spans: [{"source_document": "artifacts/iodine-metabolism-sources/8755651.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1406}] [i-met-8755651] Cloning of the mammalian type II iodothyronine deiodinase. A selenoprotein differentially expressed and regulated in human and rat brain and other tissues. (1996). https://pubmed.ncbi.nlm.nih.gov/8755651/ DOI: 10.1172/jci118806
Complete structured claim and evidence
The 3-prime-untranslated-region SECIS element was required for expression of cloned human placental DIO3, which incorporated 75Se in transfected cells.
Human DIO3 3-prime-UTR SECIS element → DIO3 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Selenium incorporation supports an enzyme that inactivates iodine-containing hormones.
evidence_locator
Primary abstract
evidence_spans
[{"source_document": "artifacts/iodine-metabolism-sources/7593630.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1405}]
experimental_model
Human placental DIO3 cDNA and heterologous expression, selenium labeling and SECIS manipulation
exposure
Cloned 2.1-kb DIO3 cDNA; 75Se labeling and SECIS-dependent expression.
limitations
Expression machinery experiment; not evidence for selenium dosing in pregnancy.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Human placental protein in transfected cells
plain_language
The hormone-inactivating enzyme also needs the cellular system that incorporates selenium into proteins.
primary_references
[i-met-7593630] Type 3 lodothyronine deiodinase: cloning, in vitro expression, and functional analysis of the placental selenoenzyme. (1995). https://pubmed.ncbi.nlm.nih.gov/7593630/ DOI: 10.1172/jci118299
tissue_or_cell_type
DIO3 expression system
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 1129–1142
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human placental DIO3 cDNA and heterologous expression, selenium labeling and SECIS manipulation · source_derived_draft · unverified_draft
### i-met-dio3-secis-expression The 3-prime-untranslated-region SECIS element was required for expression of cloned human placental DIO3, which incorporated 75Se in transfected cells. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The hormone-inactivating enzyme also needs the cellular system that incorporates selenium into proteins. organism: Human placental protein in transfected cells tissue_or_cell_type: DIO3 expression system experimental_model: Human placental DIO3 cDNA and heterologous expression, selenium labeling and SECIS manipulation limitations: Expression machinery experiment; not evidence for selenium dosing in pregnancy. exposure: Cloned 2.1-kb DIO3 cDNA; 75Se labeling and SECIS-dependent expression. cross_nutrient: Selenium incorporation supports an enzyme that inactivates iodine-containing hormones. evidence_locator: Primary abstract evidence_spans: [{"source_document": "artifacts/iodine-metabolism-sources/7593630.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1405}] [i-met-7593630] Type 3 lodothyronine deiodinase: cloning, in vitro expression, and functional analysis of the placental selenoenzyme. (1995). https://pubmed.ncbi.nlm.nih.gov/7593630/ DOI: 10.1172/jci118299
Complete structured claim and evidence
Recombinant mouse Wsb1 supported ubiquitination of human DIO2 constructs in a reconstituted assay; disruption of the Wsb1 BC box prevented this effect.
Mouse Wsb1 → DIO2 ubiquitination source_derived_draftungraded
Experimental context and source evidence
evidence_locator
Figure 1E-F; Methods: Constructs and ubiquitination assay
evidence_spans
[{"source_document": "artifacts/iodine-metabolism-sources/15965468.txt", "locator": "Figure 1E-F; Methods: Constructs and ubiquitination assay", "start_char": 13661, "end_char": 14961}]
experimental_model
HEK293 knockdown, recombinant mouse Wsb1/human DIO2 expression and ubiquitination assays; separate chicken explant experiments
exposure
Mouse Wsb1 versus BC-box mutant M1; assay contained 30 micromolar ubiquitin and 10 micromolar ubiquitin aldehyde.
limitations
Paper uses both wild-type FLAG-D2 and Sec133C/Sec266C constructs; this record concerns ubiquitination machinery, not dietary selenium dependence.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Mouse Wsb1 with human DIO2 constructs; cell-free expression system
plain_language
An ubiquitin ligase component marks DIO2 for regulation.
primary_references
[i-met-15965468] The Hedgehog-inducible ubiquitin ligase subunit WSB-1 modulates thyroid hormone activation and PTHrP secretion in the developing growth plate. (2005). https://pubmed.ncbi.nlm.nih.gov/15965468/ DOI: 10.1038/ncb1272
tissue_or_cell_type
Reconstituted ubiquitination assay
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 1144–1156
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · HEK293 knockdown, recombinant mouse Wsb1/human DIO2 expression and ubiquitination assays; separate chicken explant experiments · source_derived_draft · unverified_draft
### i-met-wsb1-dio2-ubiquitination Recombinant mouse Wsb1 supported ubiquitination of human DIO2 constructs in a reconstituted assay; disruption of the Wsb1 BC box prevented this effect. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: An ubiquitin ligase component marks DIO2 for regulation. organism: Mouse Wsb1 with human DIO2 constructs; cell-free expression system tissue_or_cell_type: Reconstituted ubiquitination assay experimental_model: HEK293 knockdown, recombinant mouse Wsb1/human DIO2 expression and ubiquitination assays; separate chicken explant experiments limitations: Paper uses both wild-type FLAG-D2 and Sec133C/Sec266C constructs; this record concerns ubiquitination machinery, not dietary selenium dependence. exposure: Mouse Wsb1 versus BC-box mutant M1; assay contained 30 micromolar ubiquitin and 10 micromolar ubiquitin aldehyde. evidence_locator: Figure 1E-F; Methods: Constructs and ubiquitination assay evidence_spans: [{"source_document": "artifacts/iodine-metabolism-sources/15965468.txt", "locator": "Figure 1E-F; Methods: Constructs and ubiquitination assay", "start_char": 13661, "end_char": 14961}] [i-met-15965468] The Hedgehog-inducible ubiquitin ligase subunit WSB-1 modulates thyroid hormone activation and PTHrP secretion in the developing growth plate. (2005). https://pubmed.ncbi.nlm.nih.gov/15965468/ DOI: 10.1038/ncb1272
Complete structured claim and evidence
WSB1 knockdown in HEK293 cells increased steady-state D2 approximately fivefold and prolonged its half-life two- to threefold.
Human WSB1 → DIO2 source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_locator
Figure 2D-G; Methods: Constructs and Transfections
evidence_spans
[{"source_document": "artifacts/iodine-metabolism-sources/15965468.txt", "locator": "Figure 2D-G; Methods: Constructs and Transfections", "start_char": 14434, "end_char": 15884}]
experimental_model
HEK293 knockdown, recombinant mouse Wsb1/human DIO2 expression and ubiquitination assays; separate chicken explant experiments
exposure
WSB1 RNA interference; activity assays used FLAG-D2, western analyses used FLAG-CysD2; turnover experiments included cycloheximide.
limitations
Wild-type and Sec-to-Cys experimental constructs have different roles; no diet was manipulated.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Human HEK293; mouse Wsb1 used in complementation arms
plain_language
Reducing the enzyme-removal machinery allows more DIO2 to remain available.
primary_references
[i-met-15965468] The Hedgehog-inducible ubiquitin ligase subunit WSB-1 modulates thyroid hormone activation and PTHrP secretion in the developing growth plate. (2005). https://pubmed.ncbi.nlm.nih.gov/15965468/ DOI: 10.1038/ncb1272
tissue_or_cell_type
Transfected HEK293 cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 1158–1170
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · HEK293 knockdown, recombinant mouse Wsb1/human DIO2 expression and ubiquitination assays; separate chicken explant experiments · source_derived_draft · unverified_draft
### i-met-wsb1-knockdown-dio2 WSB1 knockdown in HEK293 cells increased steady-state D2 approximately fivefold and prolonged its half-life two- to threefold. Condition category: machinery_impairment nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Reducing the enzyme-removal machinery allows more DIO2 to remain available. organism: Human HEK293; mouse Wsb1 used in complementation arms tissue_or_cell_type: Transfected HEK293 cells experimental_model: HEK293 knockdown, recombinant mouse Wsb1/human DIO2 expression and ubiquitination assays; separate chicken explant experiments limitations: Wild-type and Sec-to-Cys experimental constructs have different roles; no diet was manipulated. exposure: WSB1 RNA interference; activity assays used FLAG-D2, western analyses used FLAG-CysD2; turnover experiments included cycloheximide. evidence_locator: Figure 2D-G; Methods: Constructs and Transfections evidence_spans: [{"source_document": "artifacts/iodine-metabolism-sources/15965468.txt", "locator": "Figure 2D-G; Methods: Constructs and Transfections", "start_char": 14434, "end_char": 15884}] [i-met-15965468] The Hedgehog-inducible ubiquitin ligase subunit WSB-1 modulates thyroid hormone activation and PTHrP secretion in the developing growth plate. (2005). https://pubmed.ncbi.nlm.nih.gov/15965468/ DOI: 10.1038/ncb1272
Complete structured claim and evidence
T3 was bound within the human THRB ligand-binding domain in the crystallized THRB–RXRA domain heterodimer, with the THRB activation surface accommodating an SRC-2-derived peptide.
T3 → Human THRB ligand-binding domain 202–461 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
An iodine-containing hormone binds THRB in a complex with the retinoid receptor RXRA; no nutritional vitamin A manipulation.
evidence_locator
Figure 2a and Results: structural characterization; Methods: protein production and crystallography
evidence_spans
[{"source_document": "artifacts/iodine-metabolism-sources/26289479.txt", "locator": "Figure 2a and Results: structural characterization; Methods: protein production and crystallography", "start_char": 10702, "end_char": 12152}]
experimental_model
Human TR beta/RXR alpha ligand-binding-domain crystallography; full-length human receptors in CV-1 reporter assays
exposure
Human THRB residues 202–461 and RXRA residues 223–462; threefold molar excess of T3 and synthetic HKILHRLL SRC-2 peptide; structure refined at anisotropic 3.2–3.8 angstrom resolution.
limitations
Isolated domains and an eight-residue peptide, not full-length coactivator recruitment in tissue. The structure establishes binding geometry, not a physiological T3 threshold.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Human receptor domains produced in Escherichia coli; synthetic coactivator peptide
plain_language
T3 physically occupies its receptor, which presents a docking surface for a transcription coactivator.
primary_references
[i-met-26289479] Structural mechanism for signal transduction in RXR nuclear receptor heterodimers. (2015). https://pubmed.ncbi.nlm.nih.gov/26289479/ DOI: 10.1038/ncomms9013
tissue_or_cell_type
Purified receptor-domain complex
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 1172–1185
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human TR beta/RXR alpha ligand-binding-domain crystallography; full-length human receptors in CV-1 reporter assays · source_derived_draft · unverified_draft
### i-met-t3-thrb-ligand-binding T3 was bound within the human THRB ligand-binding domain in the crystallized THRB–RXRA domain heterodimer, with the THRB activation surface accommodating an SRC-2-derived peptide. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: T3 physically occupies its receptor, which presents a docking surface for a transcription coactivator. organism: Human receptor domains produced in Escherichia coli; synthetic coactivator peptide tissue_or_cell_type: Purified receptor-domain complex experimental_model: Human TR beta/RXR alpha ligand-binding-domain crystallography; full-length human receptors in CV-1 reporter assays limitations: Isolated domains and an eight-residue peptide, not full-length coactivator recruitment in tissue. The structure establishes binding geometry, not a physiological T3 threshold. exposure: Human THRB residues 202–461 and RXRA residues 223–462; threefold molar excess of T3 and synthetic HKILHRLL SRC-2 peptide; structure refined at anisotropic 3.2–3.8 angstrom resolution. cross_nutrient: An iodine-containing hormone binds THRB in a complex with the retinoid receptor RXRA; no nutritional vitamin A manipulation. evidence_locator: Figure 2a and Results: structural characterization; Methods: protein production and crystallography evidence_spans: [{"source_document": "artifacts/iodine-metabolism-sources/26289479.txt", "locator": "Figure 2a and Results: structural characterization; Methods: protein production and crystallography", "start_char": 10702, "end_char": 12152}] [i-met-26289479] Structural mechanism for signal transduction in RXR nuclear receptor heterodimers. (2015). https://pubmed.ncbi.nlm.nih.gov/26289479/ DOI: 10.1038/ncomms9013
Complete structured claim and evidence
T3 increased thyroid-response-element luciferase activity in CV-1 cells transfected with full-length human THRB and RXRA.
T3 → DR4 thyroid-response-element reporter activity source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Human thyroid and retinoid receptor machinery jointly support the measured iodine-containing-hormone response; this does not establish dietary vitamin A dependence.
evidence_locator
Figure 1b and legend; Methods: Cell-based assays
evidence_spans
[{"source_document": "artifacts/iodine-metabolism-sources/26289479.txt", "locator": "Figure 1b and legend; Methods: Cell-based assays", "start_char": 45264, "end_char": 46014}]
experimental_model
Human TR beta/RXR alpha ligand-binding-domain crystallography; full-length human receptors in CV-1 reporter assays
exposure
1 micromolar T3 for 24 hours versus vehicle, with THRB/RXRA expression plasmids and a DR4 thyroid-response luciferase reporter; quadruplicate wells and at least two experiments.
limitations
Engineered reporter and receptor overexpression; cannot infer that every endogenous gene is activated by T3 or that dietary iodine or vitamin A improves this signal.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Full-length human receptors expressed in African green monkey CV-1 cells
plain_language
Binding of the hormone can be translated into a gene-regulatory signal through its receptor.
primary_references
[i-met-26289479] Structural mechanism for signal transduction in RXR nuclear receptor heterodimers. (2015). https://pubmed.ncbi.nlm.nih.gov/26289479/ DOI: 10.1038/ncomms9013
tissue_or_cell_type
CV-1 reporter assay
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 1187–1200
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human TR beta/RXR alpha ligand-binding-domain crystallography; full-length human receptors in CV-1 reporter assays · source_derived_draft · unverified_draft
### i-met-t3-thrb-transcription T3 increased thyroid-response-element luciferase activity in CV-1 cells transfected with full-length human THRB and RXRA. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Binding of the hormone can be translated into a gene-regulatory signal through its receptor. organism: Full-length human receptors expressed in African green monkey CV-1 cells tissue_or_cell_type: CV-1 reporter assay experimental_model: Human TR beta/RXR alpha ligand-binding-domain crystallography; full-length human receptors in CV-1 reporter assays limitations: Engineered reporter and receptor overexpression; cannot infer that every endogenous gene is activated by T3 or that dietary iodine or vitamin A improves this signal. exposure: 1 micromolar T3 for 24 hours versus vehicle, with THRB/RXRA expression plasmids and a DR4 thyroid-response luciferase reporter; quadruplicate wells and at least two experiments. cross_nutrient: Human thyroid and retinoid receptor machinery jointly support the measured iodine-containing-hormone response; this does not establish dietary vitamin A dependence. evidence_locator: Figure 1b and legend; Methods: Cell-based assays evidence_spans: [{"source_document": "artifacts/iodine-metabolism-sources/26289479.txt", "locator": "Figure 1b and legend; Methods: Cell-based assays", "start_char": 45264, "end_char": 46014}] [i-met-26289479] Structural mechanism for signal transduction in RXR nuclear receptor heterodimers. (2015). https://pubmed.ncbi.nlm.nih.gov/26289479/ DOI: 10.1038/ncomms9013
Complete structured claim and evidence
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).
Iron → Thyroid volume source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
The iron and placebo groups showed no significant difference in serum thyroxine or whole-blood thyrotropin at baseline or during the intervention.
Iron → Serum total thyroxine concentration source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Mean thyroid-volume reduction at 40 weeks was 38% with dual iron–iodine salt versus 18% with iodine-only salt (P<0.01).
Iron → Thyroid volume source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
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).
Iron → Serum total thyroxine concentration source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Mean serum total T4 fell from 73.1 ± 45.4 to 48.3 ± 23.7 nmol/L after two months of selenium treatment (P<0.001) in the iodine/selenium-deficient setting.
Selenomethionine (SeMet) → Serum total thyroxine concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
true
evidence_location
Primary indexed abstract.
experimental_model
Placebo-controlled selenium intervention in 52 schoolchildren from a region of severe iodine and selenium deficiency in northern Zaire
exposure
Selenium 50 micrograms/day as selenomethionine or placebo for two months; no concurrent iodine-repletion regimen reported in the abstract.
limitations
The abstract reports before/after changes in the selenium group; do not mistake these for adjusted between-group estimates. DIO1 restoration was a proposed explanation, not directly measured. Hormone changes do not themselves establish symptomatic deterioration or a universal order for supplement treatment.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Homo sapiens
plain_language
Selenium alone lowered circulating T4 in this co-deficient population.
primary_references
[iod-clin-contempre1992] Effect of selenium supplementation on thyroid hormone metabolism in an iodine and selenium deficient population. (1992). https://pubmed.ncbi.nlm.nih.gov/1424183/ DOI: 10.1111/j.1365-2265.1992.tb02268.x
tissue_or_cell_type
Serum thyroid-hormone concentrations
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 1258–1270
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Placebo-controlled selenium intervention in 52 schoolchildren from a region of severe iodine and selenium deficiency in northern Zaire · source_derived_draft · unverified_draft
### iod-clin-selenium-total-t4 Mean serum total T4 fell from 73.1 ± 45.4 to 48.3 ± 23.7 nmol/L after two months of selenium treatment (P<0.001) in the iodine/selenium-deficient setting. Condition category: nutrient_deficiency nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Selenium alone lowered circulating T4 in this co-deficient population. organism: Homo sapiens tissue_or_cell_type: Serum thyroid-hormone concentrations experimental_model: Placebo-controlled selenium intervention in 52 schoolchildren from a region of severe iodine and selenium deficiency in northern Zaire limitations: The abstract reports before/after changes in the selenium group; do not mistake these for adjusted between-group estimates. DIO1 restoration was a proposed explanation, not directly measured. Hormone changes do not themselves establish symptomatic deterioration or a universal order for supplement treatment. exposure: Selenium 50 micrograms/day as selenomethionine or placebo for two months; no concurrent iodine-repletion regimen reported in the abstract. cross_nutrient: true evidence_location: Primary indexed abstract. [iod-clin-contempre1992] Effect of selenium supplementation on thyroid hormone metabolism in an iodine and selenium deficient population. (1992). https://pubmed.ncbi.nlm.nih.gov/1424183/ DOI: 10.1111/j.1365-2265.1992.tb02268.x
Complete structured claim and evidence
Mean serum free T4 fell from 11.8 ± 6.7 to 8.4 ± 4.1 pmol/L after selenium treatment (P<0.01).
Selenomethionine (SeMet) → Serum free thyroxine concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
true
evidence_location
Primary indexed abstract.
experimental_model
Placebo-controlled selenium intervention in 52 schoolchildren from a region of severe iodine and selenium deficiency in northern Zaire
exposure
Selenium 50 micrograms/day as selenomethionine or placebo for two months; no concurrent iodine-repletion regimen reported in the abstract.
limitations
The abstract reports before/after changes in the selenium group; do not mistake these for adjusted between-group estimates. DIO1 restoration was a proposed explanation, not directly measured. Hormone changes do not themselves establish symptomatic deterioration or a universal order for supplement treatment.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Homo sapiens
plain_language
The free T4 measurement also fell after selenium was added.
primary_references
[iod-clin-contempre1992] Effect of selenium supplementation on thyroid hormone metabolism in an iodine and selenium deficient population. (1992). https://pubmed.ncbi.nlm.nih.gov/1424183/ DOI: 10.1111/j.1365-2265.1992.tb02268.x
tissue_or_cell_type
Serum thyroid-hormone concentrations
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 1272–1284
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Placebo-controlled selenium intervention in 52 schoolchildren from a region of severe iodine and selenium deficiency in northern Zaire · source_derived_draft · unverified_draft
### iod-clin-selenium-free-t4 Mean serum free T4 fell from 11.8 ± 6.7 to 8.4 ± 4.1 pmol/L after selenium treatment (P<0.01). Condition category: nutrient_deficiency nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The free T4 measurement also fell after selenium was added. organism: Homo sapiens tissue_or_cell_type: Serum thyroid-hormone concentrations experimental_model: Placebo-controlled selenium intervention in 52 schoolchildren from a region of severe iodine and selenium deficiency in northern Zaire limitations: The abstract reports before/after changes in the selenium group; do not mistake these for adjusted between-group estimates. DIO1 restoration was a proposed explanation, not directly measured. Hormone changes do not themselves establish symptomatic deterioration or a universal order for supplement treatment. exposure: Selenium 50 micrograms/day as selenomethionine or placebo for two months; no concurrent iodine-repletion regimen reported in the abstract. cross_nutrient: true evidence_location: Primary indexed abstract. [iod-clin-contempre1992] Effect of selenium supplementation on thyroid hormone metabolism in an iodine and selenium deficient population. (1992). https://pubmed.ncbi.nlm.nih.gov/1424183/ DOI: 10.1111/j.1365-2265.1992.tb02268.x
Complete structured claim and evidence
Mean reverse T3 fell from 124 ± 115 to 90 ± 72 pmol/L after selenium treatment (P<0.05), while serum T3 and TSH did not change significantly.
Selenomethionine (SeMet) → Serum reverse T3 concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
true
evidence_location
Primary indexed abstract.
experimental_model
Placebo-controlled selenium intervention in 52 schoolchildren from a region of severe iodine and selenium deficiency in northern Zaire
exposure
Selenium 50 micrograms/day as selenomethionine or placebo for two months; no concurrent iodine-repletion regimen reported in the abstract.
limitations
The abstract reports before/after changes in the selenium group; do not mistake these for adjusted between-group estimates. DIO1 restoration was a proposed explanation, not directly measured. Hormone changes do not themselves establish symptomatic deterioration or a universal order for supplement treatment.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Homo sapiens
plain_language
The hormone pattern changed unevenly; T3 and TSH did not simply rise with selenium.
primary_references
[iod-clin-contempre1992] Effect of selenium supplementation on thyroid hormone metabolism in an iodine and selenium deficient population. (1992). https://pubmed.ncbi.nlm.nih.gov/1424183/ DOI: 10.1111/j.1365-2265.1992.tb02268.x
tissue_or_cell_type
Serum thyroid-hormone concentrations
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 1286–1298
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Placebo-controlled selenium intervention in 52 schoolchildren from a region of severe iodine and selenium deficiency in northern Zaire · source_derived_draft · unverified_draft
### iod-clin-selenium-rt3 Mean reverse T3 fell from 124 ± 115 to 90 ± 72 pmol/L after selenium treatment (P<0.05), while serum T3 and TSH did not change significantly. Condition category: nutrient_deficiency nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The hormone pattern changed unevenly; T3 and TSH did not simply rise with selenium. organism: Homo sapiens tissue_or_cell_type: Serum thyroid-hormone concentrations experimental_model: Placebo-controlled selenium intervention in 52 schoolchildren from a region of severe iodine and selenium deficiency in northern Zaire limitations: The abstract reports before/after changes in the selenium group; do not mistake these for adjusted between-group estimates. DIO1 restoration was a proposed explanation, not directly measured. Hormone changes do not themselves establish symptomatic deterioration or a universal order for supplement treatment. exposure: Selenium 50 micrograms/day as selenomethionine or placebo for two months; no concurrent iodine-repletion regimen reported in the abstract. cross_nutrient: true evidence_location: Primary indexed abstract. [iod-clin-contempre1992] Effect of selenium supplementation on thyroid hormone metabolism in an iodine and selenium deficient population. (1992). https://pubmed.ncbi.nlm.nih.gov/1424183/ DOI: 10.1111/j.1365-2265.1992.tb02268.x
Complete structured claim and evidence
At 24 weeks, mean total T4 in iodine-treated children was approximately 40% higher than baseline and hypothyroxinemia prevalence was below 1%; corresponding placebo-group status did not improve significantly.
Iodized oil preparation → Serum total thyroxine concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
false
evidence_location
Primary full PDF Methods, Results, Tables 1–2 and Discussion, pp.108–114.
experimental_model
Randomized double-blind placebo-controlled 24-week trial in 310 moderately iodine-deficient Albanian children aged 10–12
exposure
One supervised oral dose of iodized poppyseed oil containing 400 mg iodine versus sunflower-oil placebo; baseline median urinary iodine 43 micrograms/L, 87% goitrous; iodine 159/placebo 151 randomized.
limitations
Baseline groups differed on four psychological tests; analyses adjusted for baseline score, school and sex. Follow-up was 24 weeks, with no proof of lasting IQ or school-performance improvement. Symbol-search test-retest reliability was modest. Dose is a historical depot intervention, not daily intake. The 40% figure is a within-treatment change described in the abstract, not a verified adjusted between-group estimate.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Homo sapiens
plain_language
Iodine repletion restored thyroid hormone status in these moderately deficient children.
primary_references
[iod-clin-albania2006] Iodine supplementation improves cognition in iodine-deficient schoolchildren in Albania: a randomized, controlled, double-blind study. (2006). https://pubmed.ncbi.nlm.nih.gov/16400058/ DOI: 10.1093/ajcn/83.1.108
tissue_or_cell_type
Thyroid hormones and cognitive/motor testing
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 1300–1312
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 24-week trial in 310 moderately iodine-deficient Albanian children aged 10–12 · source_derived_draft · unverified_draft
### iod-clin-albania-thyroxine At 24 weeks, mean total T4 in iodine-treated children was approximately 40% higher than baseline and hypothyroxinemia prevalence was below 1%; corresponding placebo-group status did not improve significantly. Condition category: nutrient_deficiency nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Iodine repletion restored thyroid hormone status in these moderately deficient children. organism: Homo sapiens tissue_or_cell_type: Thyroid hormones and cognitive/motor testing experimental_model: Randomized double-blind placebo-controlled 24-week trial in 310 moderately iodine-deficient Albanian children aged 10–12 limitations: Baseline groups differed on four psychological tests; analyses adjusted for baseline score, school and sex. Follow-up was 24 weeks, with no proof of lasting IQ or school-performance improvement. Symbol-search test-retest reliability was modest. Dose is a historical depot intervention, not daily intake. The 40% figure is a within-treatment change described in the abstract, not a verified adjusted between-group estimate. exposure: One supervised oral dose of iodized poppyseed oil containing 400 mg iodine versus sunflower-oil placebo; baseline median urinary iodine 43 micrograms/L, 87% goitrous; iodine 159/placebo 151 randomized. cross_nutrient: false evidence_location: Primary full PDF Methods, Results, Tables 1–2 and Discussion, pp.108–114. [iod-clin-albania2006] Iodine supplementation improves cognition in iodine-deficient schoolchildren in Albania: a randomized, controlled, double-blind study. (2006). https://pubmed.ncbi.nlm.nih.gov/16400058/ DOI: 10.1093/ajcn/83.1.108
Complete structured claim and evidence
Iodine treatment improved rapid target marking performance compared with placebo at 24 weeks (reported adjusted P<0.0001).
Iodized oil preparation → Rapid target-marking performance source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
false
evidence_location
Primary full PDF Methods, Results, Tables 1–2 and Discussion, pp.108–114.
experimental_model
Randomized double-blind placebo-controlled 24-week trial in 310 moderately iodine-deficient Albanian children aged 10–12
exposure
One supervised oral dose of iodized poppyseed oil containing 400 mg iodine versus sunflower-oil placebo; baseline median urinary iodine 43 micrograms/L, 87% goitrous; iodine 159/placebo 151 randomized.
limitations
Baseline groups differed on four psychological tests; analyses adjusted for baseline score, school and sex. Follow-up was 24 weeks, with no proof of lasting IQ or school-performance improvement. Symbol-search test-retest reliability was modest. Dose is a historical depot intervention, not daily intake. One of four improved tests in a seven-test battery; a positive result on this task is not an effect size for general intelligence.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Homo sapiens
plain_language
In this study, iodine repletion improved rapid target marking.
primary_references
[iod-clin-albania2006] Iodine supplementation improves cognition in iodine-deficient schoolchildren in Albania: a randomized, controlled, double-blind study. (2006). https://pubmed.ncbi.nlm.nih.gov/16400058/ DOI: 10.1093/ajcn/83.1.108
tissue_or_cell_type
Thyroid hormones and cognitive/motor testing
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Iodine: thyroid hormone production, deficiency, excess 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 · Randomized double-blind placebo-controlled 24-week trial in 310 moderately iodine-deficient Albanian children aged 10–12 · source_derived_draft · unverified_draft
### iod-clin-albania-target Iodine treatment improved rapid target marking performance compared with placebo at 24 weeks (reported adjusted P<0.0001). Condition category: nutrient_deficiency nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: In this study, iodine repletion improved rapid target marking. organism: Homo sapiens tissue_or_cell_type: Thyroid hormones and cognitive/motor testing experimental_model: Randomized double-blind placebo-controlled 24-week trial in 310 moderately iodine-deficient Albanian children aged 10–12 limitations: Baseline groups differed on four psychological tests; analyses adjusted for baseline score, school and sex. Follow-up was 24 weeks, with no proof of lasting IQ or school-performance improvement. Symbol-search test-retest reliability was modest. Dose is a historical depot intervention, not daily intake. One of four improved tests in a seven-test battery; a positive result on this task is not an effect size for general intelligence. exposure: One supervised oral dose of iodized poppyseed oil containing 400 mg iodine versus sunflower-oil placebo; baseline median urinary iodine 43 micrograms/L, 87% goitrous; iodine 159/placebo 151 randomized. cross_nutrient: false evidence_location: Primary full PDF Methods, Results, Tables 1–2 and Discussion, pp.108–114. [iod-clin-albania2006] Iodine supplementation improves cognition in iodine-deficient schoolchildren in Albania: a randomized, controlled, double-blind study. (2006). https://pubmed.ncbi.nlm.nih.gov/16400058/ DOI: 10.1093/ajcn/83.1.108
Complete structured claim and evidence
Iodine treatment improved symbol search performance compared with placebo at 24 weeks (reported adjusted P<0.0001).
Iodized oil preparation → Symbol-search performance source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
false
evidence_location
Primary full PDF Methods, Results, Tables 1–2 and Discussion, pp.108–114.
experimental_model
Randomized double-blind placebo-controlled 24-week trial in 310 moderately iodine-deficient Albanian children aged 10–12
exposure
One supervised oral dose of iodized poppyseed oil containing 400 mg iodine versus sunflower-oil placebo; baseline median urinary iodine 43 micrograms/L, 87% goitrous; iodine 159/placebo 151 randomized.
limitations
Baseline groups differed on four psychological tests; analyses adjusted for baseline score, school and sex. Follow-up was 24 weeks, with no proof of lasting IQ or school-performance improvement. Symbol-search test-retest reliability was modest. Dose is a historical depot intervention, not daily intake. One of four improved tests in a seven-test battery; a positive result on this task is not an effect size for general intelligence.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Homo sapiens
plain_language
In this study, iodine repletion improved symbol search.
primary_references
[iod-clin-albania2006] Iodine supplementation improves cognition in iodine-deficient schoolchildren in Albania: a randomized, controlled, double-blind study. (2006). https://pubmed.ncbi.nlm.nih.gov/16400058/ DOI: 10.1093/ajcn/83.1.108
tissue_or_cell_type
Thyroid hormones and cognitive/motor testing
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 1328–1340
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 24-week trial in 310 moderately iodine-deficient Albanian children aged 10–12 · source_derived_draft · unverified_draft
### iod-clin-albania-symbol Iodine treatment improved symbol search performance compared with placebo at 24 weeks (reported adjusted P<0.0001). Condition category: nutrient_deficiency nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: In this study, iodine repletion improved symbol search. organism: Homo sapiens tissue_or_cell_type: Thyroid hormones and cognitive/motor testing experimental_model: Randomized double-blind placebo-controlled 24-week trial in 310 moderately iodine-deficient Albanian children aged 10–12 limitations: Baseline groups differed on four psychological tests; analyses adjusted for baseline score, school and sex. Follow-up was 24 weeks, with no proof of lasting IQ or school-performance improvement. Symbol-search test-retest reliability was modest. Dose is a historical depot intervention, not daily intake. One of four improved tests in a seven-test battery; a positive result on this task is not an effect size for general intelligence. exposure: One supervised oral dose of iodized poppyseed oil containing 400 mg iodine versus sunflower-oil placebo; baseline median urinary iodine 43 micrograms/L, 87% goitrous; iodine 159/placebo 151 randomized. cross_nutrient: false evidence_location: Primary full PDF Methods, Results, Tables 1–2 and Discussion, pp.108–114. [iod-clin-albania2006] Iodine supplementation improves cognition in iodine-deficient schoolchildren in Albania: a randomized, controlled, double-blind study. (2006). https://pubmed.ncbi.nlm.nih.gov/16400058/ DOI: 10.1093/ajcn/83.1.108
Complete structured claim and evidence
Iodine treatment improved rapid object naming performance compared with placebo at 24 weeks (reported adjusted P<0.0001).
Iodized oil preparation → Rapid object-naming performance source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
false
evidence_location
Primary full PDF Methods, Results, Tables 1–2 and Discussion, pp.108–114.
experimental_model
Randomized double-blind placebo-controlled 24-week trial in 310 moderately iodine-deficient Albanian children aged 10–12
exposure
One supervised oral dose of iodized poppyseed oil containing 400 mg iodine versus sunflower-oil placebo; baseline median urinary iodine 43 micrograms/L, 87% goitrous; iodine 159/placebo 151 randomized.
limitations
Baseline groups differed on four psychological tests; analyses adjusted for baseline score, school and sex. Follow-up was 24 weeks, with no proof of lasting IQ or school-performance improvement. Symbol-search test-retest reliability was modest. Dose is a historical depot intervention, not daily intake. One of four improved tests in a seven-test battery; a positive result on this task is not an effect size for general intelligence.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Homo sapiens
plain_language
In this study, iodine repletion improved rapid object naming.
primary_references
[iod-clin-albania2006] Iodine supplementation improves cognition in iodine-deficient schoolchildren in Albania: a randomized, controlled, double-blind study. (2006). https://pubmed.ncbi.nlm.nih.gov/16400058/ DOI: 10.1093/ajcn/83.1.108
tissue_or_cell_type
Thyroid hormones and cognitive/motor testing
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 1342–1354
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 24-week trial in 310 moderately iodine-deficient Albanian children aged 10–12 · source_derived_draft · unverified_draft
### iod-clin-albania-naming Iodine treatment improved rapid object naming performance compared with placebo at 24 weeks (reported adjusted P<0.0001). Condition category: nutrient_deficiency nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: In this study, iodine repletion improved rapid object naming. organism: Homo sapiens tissue_or_cell_type: Thyroid hormones and cognitive/motor testing experimental_model: Randomized double-blind placebo-controlled 24-week trial in 310 moderately iodine-deficient Albanian children aged 10–12 limitations: Baseline groups differed on four psychological tests; analyses adjusted for baseline score, school and sex. Follow-up was 24 weeks, with no proof of lasting IQ or school-performance improvement. Symbol-search test-retest reliability was modest. Dose is a historical depot intervention, not daily intake. One of four improved tests in a seven-test battery; a positive result on this task is not an effect size for general intelligence. exposure: One supervised oral dose of iodized poppyseed oil containing 400 mg iodine versus sunflower-oil placebo; baseline median urinary iodine 43 micrograms/L, 87% goitrous; iodine 159/placebo 151 randomized. cross_nutrient: false evidence_location: Primary full PDF Methods, Results, Tables 1–2 and Discussion, pp.108–114. [iod-clin-albania2006] Iodine supplementation improves cognition in iodine-deficient schoolchildren in Albania: a randomized, controlled, double-blind study. (2006). https://pubmed.ncbi.nlm.nih.gov/16400058/ DOI: 10.1093/ajcn/83.1.108
Complete structured claim and evidence
Iodine treatment improved Raven’s Coloured Progressive Matrices performance compared with placebo at 24 weeks (reported adjusted P<0.0001).
Iodized oil preparation → Raven Coloured Progressive Matrices performance source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
false
evidence_location
Primary full PDF Methods, Results, Tables 1–2 and Discussion, pp.108–114.
experimental_model
Randomized double-blind placebo-controlled 24-week trial in 310 moderately iodine-deficient Albanian children aged 10–12
exposure
One supervised oral dose of iodized poppyseed oil containing 400 mg iodine versus sunflower-oil placebo; baseline median urinary iodine 43 micrograms/L, 87% goitrous; iodine 159/placebo 151 randomized.
limitations
Baseline groups differed on four psychological tests; analyses adjusted for baseline score, school and sex. Follow-up was 24 weeks, with no proof of lasting IQ or school-performance improvement. Symbol-search test-retest reliability was modest. Dose is a historical depot intervention, not daily intake. One of four improved tests in a seven-test battery; a positive result on this task is not an effect size for general intelligence.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Homo sapiens
plain_language
In this study, iodine repletion improved Raven’s Coloured Progressive Matrices.
primary_references
[iod-clin-albania2006] Iodine supplementation improves cognition in iodine-deficient schoolchildren in Albania: a randomized, controlled, double-blind study. (2006). https://pubmed.ncbi.nlm.nih.gov/16400058/ DOI: 10.1093/ajcn/83.1.108
tissue_or_cell_type
Thyroid hormones and cognitive/motor testing
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 1356–1368
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 24-week trial in 310 moderately iodine-deficient Albanian children aged 10–12 · source_derived_draft · unverified_draft
### iod-clin-albania-raven Iodine treatment improved Raven’s Coloured Progressive Matrices performance compared with placebo at 24 weeks (reported adjusted P<0.0001). Condition category: nutrient_deficiency nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: In this study, iodine repletion improved Raven’s Coloured Progressive Matrices. organism: Homo sapiens tissue_or_cell_type: Thyroid hormones and cognitive/motor testing experimental_model: Randomized double-blind placebo-controlled 24-week trial in 310 moderately iodine-deficient Albanian children aged 10–12 limitations: Baseline groups differed on four psychological tests; analyses adjusted for baseline score, school and sex. Follow-up was 24 weeks, with no proof of lasting IQ or school-performance improvement. Symbol-search test-retest reliability was modest. Dose is a historical depot intervention, not daily intake. One of four improved tests in a seven-test battery; a positive result on this task is not an effect size for general intelligence. exposure: One supervised oral dose of iodized poppyseed oil containing 400 mg iodine versus sunflower-oil placebo; baseline median urinary iodine 43 micrograms/L, 87% goitrous; iodine 159/placebo 151 randomized. cross_nutrient: false evidence_location: Primary full PDF Methods, Results, Tables 1–2 and Discussion, pp.108–114. [iod-clin-albania2006] Iodine supplementation improves cognition in iodine-deficient schoolchildren in Albania: a randomized, controlled, double-blind study. (2006). https://pubmed.ncbi.nlm.nih.gov/16400058/ DOI: 10.1093/ajcn/83.1.108
Complete structured claim and evidence
Verbal IQ at 5–6 years averaged 89.5 versus 90.2 with maternal iodine versus placebo; reported difference −0.7 (95% CI −2.9 to 1.5), P=0.77.
Potassium iodide → Child WPPSI-III verbal IQ score source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
false
evidence_location
Primary full PDF Methods; Table2 and Fig2; Discussion, pp.853–863.
experimental_model
Randomized double-blind placebo-controlled maternal trial in Bangkok and Bangalore; 832 women randomized, 313 children assessed for IQ and 315 for executive function at age 5–6
exposure
200 micrograms iodine/day as potassium iodide until delivery; mean enrollment 10.7 weeks gestation; baseline median urinary iodine 131 micrograms/L; IQ iodine 159/placebo 154, executive function 159/156.
limitations
Mild group-level deficiency with site differences: Thailand deficient and India at low adequacy. Substantial attrition was balanced between groups; measured baseline characteristics were similar in those followed and lost. This does not test preconception treatment or severe deficiency. Reported differences, CIs and mixed-model P values are retained as published.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Homo sapiens
plain_language
Starting iodine during this mildly deficient pregnancy trial did not significantly improve verbal IQ.
primary_references
[iod-clin-gow2017] Effect of iodine supplementation in pregnant women on child neurodevelopment: a randomised, double-blind, placebo-controlled trial. (2017). https://pubmed.ncbi.nlm.nih.gov/29030199/ DOI: 10.1016/s2213-8587(17)30332-7
tissue_or_cell_type
Maternal iodine status and child neurodevelopment
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 1370–1382
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 maternal trial in Bangkok and Bangalore; 832 women randomized, 313 children assessed for IQ and 315 for executive function at age 5–6 · source_derived_draft · unverified_draft
### iod-clin-pregnancy-verbal Verbal IQ at 5–6 years averaged 89.5 versus 90.2 with maternal iodine versus placebo; reported difference −0.7 (95% CI −2.9 to 1.5), P=0.77. Condition category: nutrient_deficiency nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Starting iodine during this mildly deficient pregnancy trial did not significantly improve verbal IQ. organism: Homo sapiens tissue_or_cell_type: Maternal iodine status and child neurodevelopment experimental_model: Randomized double-blind placebo-controlled maternal trial in Bangkok and Bangalore; 832 women randomized, 313 children assessed for IQ and 315 for executive function at age 5–6 limitations: Mild group-level deficiency with site differences: Thailand deficient and India at low adequacy. Substantial attrition was balanced between groups; measured baseline characteristics were similar in those followed and lost. This does not test preconception treatment or severe deficiency. Reported differences, CIs and mixed-model P values are retained as published. exposure: 200 micrograms iodine/day as potassium iodide until delivery; mean enrollment 10.7 weeks gestation; baseline median urinary iodine 131 micrograms/L; IQ iodine 159/placebo 154, executive function 159/156. cross_nutrient: false evidence_location: Primary full PDF Methods; Table2 and Fig2; Discussion, pp.853–863. [iod-clin-gow2017] Effect of iodine supplementation in pregnant women on child neurodevelopment: a randomised, double-blind, placebo-controlled trial. (2017). https://pubmed.ncbi.nlm.nih.gov/29030199/ DOI: 10.1016/s2213-8587(17)30332-7
Complete structured claim and evidence
Performance IQ averaged 97.5 versus 99.1; reported iodine-minus-placebo difference −1.6 (95% CI −4.5 to 1.3), P=0.44.
Potassium iodide → Child WPPSI-III performance IQ score source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
false
evidence_location
Primary full PDF Methods; Table2 and Fig2; Discussion, pp.853–863.
experimental_model
Randomized double-blind placebo-controlled maternal trial in Bangkok and Bangalore; 832 women randomized, 313 children assessed for IQ and 315 for executive function at age 5–6
exposure
200 micrograms iodine/day as potassium iodide until delivery; mean enrollment 10.7 weeks gestation; baseline median urinary iodine 131 micrograms/L; IQ iodine 159/placebo 154, executive function 159/156.
limitations
Mild group-level deficiency with site differences: Thailand deficient and India at low adequacy. Substantial attrition was balanced between groups; measured baseline characteristics were similar in those followed and lost. This does not test preconception treatment or severe deficiency. Reported differences, CIs and mixed-model P values are retained as published.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Homo sapiens
plain_language
The performance-IQ endpoint also showed no significant improvement.
primary_references
[iod-clin-gow2017] Effect of iodine supplementation in pregnant women on child neurodevelopment: a randomised, double-blind, placebo-controlled trial. (2017). https://pubmed.ncbi.nlm.nih.gov/29030199/ DOI: 10.1016/s2213-8587(17)30332-7
tissue_or_cell_type
Maternal iodine status and child neurodevelopment
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 1384–1396
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 maternal trial in Bangkok and Bangalore; 832 women randomized, 313 children assessed for IQ and 315 for executive function at age 5–6 · source_derived_draft · unverified_draft
### iod-clin-pregnancy-performance Performance IQ averaged 97.5 versus 99.1; reported iodine-minus-placebo difference −1.6 (95% CI −4.5 to 1.3), P=0.44. Condition category: nutrient_deficiency nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The performance-IQ endpoint also showed no significant improvement. organism: Homo sapiens tissue_or_cell_type: Maternal iodine status and child neurodevelopment experimental_model: Randomized double-blind placebo-controlled maternal trial in Bangkok and Bangalore; 832 women randomized, 313 children assessed for IQ and 315 for executive function at age 5–6 limitations: Mild group-level deficiency with site differences: Thailand deficient and India at low adequacy. Substantial attrition was balanced between groups; measured baseline characteristics were similar in those followed and lost. This does not test preconception treatment or severe deficiency. Reported differences, CIs and mixed-model P values are retained as published. exposure: 200 micrograms iodine/day as potassium iodide until delivery; mean enrollment 10.7 weeks gestation; baseline median urinary iodine 131 micrograms/L; IQ iodine 159/placebo 154, executive function 159/156. cross_nutrient: false evidence_location: Primary full PDF Methods; Table2 and Fig2; Discussion, pp.853–863. [iod-clin-gow2017] Effect of iodine supplementation in pregnant women on child neurodevelopment: a randomised, double-blind, placebo-controlled trial. (2017). https://pubmed.ncbi.nlm.nih.gov/29030199/ DOI: 10.1016/s2213-8587(17)30332-7
Complete structured claim and evidence
The BRIEF-P global executive score averaged 90.6 versus 91.5; reported difference −0.9 (95% CI −6.8 to 5.0), P=0.74.
Potassium iodide → Child BRIEF-P global executive composite score source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
false
evidence_location
Primary full PDF Methods; Table2 and Fig2; Discussion, pp.853–863.
experimental_model
Randomized double-blind placebo-controlled maternal trial in Bangkok and Bangalore; 832 women randomized, 313 children assessed for IQ and 315 for executive function at age 5–6
exposure
200 micrograms iodine/day as potassium iodide until delivery; mean enrollment 10.7 weeks gestation; baseline median urinary iodine 131 micrograms/L; IQ iodine 159/placebo 154, executive function 159/156.
limitations
Mild group-level deficiency with site differences: Thailand deficient and India at low adequacy. Substantial attrition was balanced between groups; measured baseline characteristics were similar in those followed and lost. This does not test preconception treatment or severe deficiency. Reported differences, CIs and mixed-model P values are retained as published.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Homo sapiens
plain_language
Executive-function scores did not significantly differ between the trial groups.
primary_references
[iod-clin-gow2017] Effect of iodine supplementation in pregnant women on child neurodevelopment: a randomised, double-blind, placebo-controlled trial. (2017). https://pubmed.ncbi.nlm.nih.gov/29030199/ DOI: 10.1016/s2213-8587(17)30332-7
tissue_or_cell_type
Maternal iodine status and child neurodevelopment
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 1398–1410
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 maternal trial in Bangkok and Bangalore; 832 women randomized, 313 children assessed for IQ and 315 for executive function at age 5–6 · source_derived_draft · unverified_draft
### iod-clin-pregnancy-executive The BRIEF-P global executive score averaged 90.6 versus 91.5; reported difference −0.9 (95% CI −6.8 to 5.0), P=0.74. Condition category: nutrient_deficiency nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Executive-function scores did not significantly differ between the trial groups. organism: Homo sapiens tissue_or_cell_type: Maternal iodine status and child neurodevelopment experimental_model: Randomized double-blind placebo-controlled maternal trial in Bangkok and Bangalore; 832 women randomized, 313 children assessed for IQ and 315 for executive function at age 5–6 limitations: Mild group-level deficiency with site differences: Thailand deficient and India at low adequacy. Substantial attrition was balanced between groups; measured baseline characteristics were similar in those followed and lost. This does not test preconception treatment or severe deficiency. Reported differences, CIs and mixed-model P values are retained as published. exposure: 200 micrograms iodine/day as potassium iodide until delivery; mean enrollment 10.7 weeks gestation; baseline median urinary iodine 131 micrograms/L; IQ iodine 159/placebo 154, executive function 159/156. cross_nutrient: false evidence_location: Primary full PDF Methods; Table2 and Fig2; Discussion, pp.853–863. [iod-clin-gow2017] Effect of iodine supplementation in pregnant women on child neurodevelopment: a randomised, double-blind, placebo-controlled trial. (2017). https://pubmed.ncbi.nlm.nih.gov/29030199/ DOI: 10.1016/s2213-8587(17)30332-7
Complete structured claim and evidence
Among children conceived after maternal trial entry, the follow-up classified 0 of 237 in the iodinated-oil group and 14 of 215 in the saline group as definite cases of the historical neurological iodine-deficiency syndrome.
Iodized oil preparation → Severe prenatal iodine-deficiency neurological syndrome source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
false
evidence_location
Primary PDF Methods p.69, Results and Fig2 pp.70–71; relevant pages visually inspected because OCR is imperfect.
experimental_model
Historical double-blind controlled maternal iodinated-oil trial begun 1966, with children born 1966–1972 followed through 1982 in five selected Papua New Guinea villages
exposure
Intramuscular iodinated oil versus saline; comparison by conception before/after maternal trial entry. The follow-up paper does not verify the injection dose in the inspected methods.
limitations
Long-term follow-up was restricted for logistical reasons to five of 13 original villages with high disease prevalence. Historical syndrome criteria and selection differ from modern mild-deficiency trials. Do not assume all developmental disorders were prevented or that established deficits were reversed. Two possible cases remained among the 237 treated-group children. Three definite treated-group cases in the overall 274 children had maternal treatment only at 30, 32 or 34 weeks gestation; this does not establish an exact universal gestational cutoff.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Homo sapiens
plain_language
In severe deficiency, supplying iodine before conception prevented the study-defined definite neurological syndrome in this follow-up.
primary_references
[iod-clin-pharoah1987] A controlled trial of iodinated oil for the prevention of endemic cretinism: a long-term follow-up. (1987). https://pubmed.ncbi.nlm.nih.gov/3032814/ DOI: 10.1093/ije/16.1.68
tissue_or_cell_type
Child neurological, hearing/speech and motor outcomes
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 1412–1424
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Historical double-blind controlled maternal iodinated-oil trial begun 1966, with children born 1966–1972 followed through 1982 in five selected Papua New Guinea villages · source_derived_draft · unverified_draft
### iod-clin-preconception-neurology Among children conceived after maternal trial entry, the follow-up classified 0 of 237 in the iodinated-oil group and 14 of 215 in the saline group as definite cases of the historical neurological iodine-deficiency syndrome. Condition category: nutrient_deficiency nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: In severe deficiency, supplying iodine before conception prevented the study-defined definite neurological syndrome in this follow-up. organism: Homo sapiens tissue_or_cell_type: Child neurological, hearing/speech and motor outcomes experimental_model: Historical double-blind controlled maternal iodinated-oil trial begun 1966, with children born 1966–1972 followed through 1982 in five selected Papua New Guinea villages limitations: Long-term follow-up was restricted for logistical reasons to five of 13 original villages with high disease prevalence. Historical syndrome criteria and selection differ from modern mild-deficiency trials. Do not assume all developmental disorders were prevented or that established deficits were reversed. Two possible cases remained among the 237 treated-group children. Three definite treated-group cases in the overall 274 children had maternal treatment only at 30, 32 or 34 weeks gestation; this does not establish an exact universal gestational cutoff. exposure: Intramuscular iodinated oil versus saline; comparison by conception before/after maternal trial entry. The follow-up paper does not verify the injection dose in the inspected methods. cross_nutrient: false evidence_location: Primary PDF Methods p.69, Results and Fig2 pp.70–71; relevant pages visually inspected because OCR is imperfect. [iod-clin-pharoah1987] A controlled trial of iodinated oil for the prevention of endemic cretinism: a long-term follow-up. (1987). https://pubmed.ncbi.nlm.nih.gov/3032814/ DOI: 10.1093/ije/16.1.68
Complete structured claim and evidence
Mean within-person variability was 32% for measured 24-hour iodine excretion, 33% for estimated 24-hour excretion and 38% for spot urinary iodine concentration.
Urinary iodine concentration → Twenty-four-hour urinary iodine excretion source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
cross_nutrient
false
evidence_location
Primary indexed abstract.
experimental_model
Prospective 15-month repeated-collection study in 22 healthy Swiss women aged 52–77
exposure
341 24-hour urine collections and 177 corresponding fasting second-void morning spot samples; within-person variability used for precision estimates.
limitations
The sample-number estimate is specific to this population, sampling method and 20% precision target. It is not a universal instruction to collect ten specimens or a validated single-person diagnostic cutoff.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Homo sapiens
plain_language
One urine result can vary substantially within the same person.
primary_references
[iod-clin-konig2011] Ten repeat collections for urinary iodine from spot samples or 24-hour samples are needed to reliably estimate individual iodine status in women. (2011). https://pubmed.ncbi.nlm.nih.gov/21918061/ DOI: 10.3945/jn.111.144071
tissue_or_cell_type
Spot and24-hour urine
trigger_kind
biomarker_context Imported condition classification; unverified.
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 1426–1438
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Prospective 15-month repeated-collection study in 22 healthy Swiss women aged 52–77 · source_derived_draft · unverified_draft
### iod-clin-urine-variability Mean within-person variability was 32% for measured 24-hour iodine excretion, 33% for estimated 24-hour excretion and 38% for spot urinary iodine concentration. Condition category: biomarker_context nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: One urine result can vary substantially within the same person. organism: Homo sapiens tissue_or_cell_type: Spot and24-hour urine experimental_model: Prospective 15-month repeated-collection study in 22 healthy Swiss women aged 52–77 limitations: The sample-number estimate is specific to this population, sampling method and 20% precision target. It is not a universal instruction to collect ten specimens or a validated single-person diagnostic cutoff. exposure: 341 24-hour urine collections and 177 corresponding fasting second-void morning spot samples; within-person variability used for precision estimates. cross_nutrient: false evidence_location: Primary indexed abstract. [iod-clin-konig2011] Ten repeat collections for urinary iodine from spot samples or 24-hour samples are needed to reliably estimate individual iodine status in women. (2011). https://pubmed.ncbi.nlm.nih.gov/21918061/ DOI: 10.3945/jn.111.144071
Complete structured claim and evidence
The study estimated that 10 spot or 24-hour collections were needed to estimate individual iodine status with 20% precision in these women.
Urinary iodine concentration → Twenty-four-hour urinary iodine excretion source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
cross_nutrient
false
evidence_location
Primary indexed abstract.
experimental_model
Prospective 15-month repeated-collection study in 22 healthy Swiss women aged 52–77
exposure
341 24-hour urine collections and 177 corresponding fasting second-void morning spot samples; within-person variability used for precision estimates.
limitations
The sample-number estimate is specific to this population, sampling method and 20% precision target. It is not a universal instruction to collect ten specimens or a validated single-person diagnostic cutoff.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Homo sapiens
plain_language
The precision calculation required repeated samples, not a single diagnostic urine value.
primary_references
[iod-clin-konig2011] Ten repeat collections for urinary iodine from spot samples or 24-hour samples are needed to reliably estimate individual iodine status in women. (2011). https://pubmed.ncbi.nlm.nih.gov/21918061/ DOI: 10.3945/jn.111.144071
tissue_or_cell_type
Spot and24-hour urine
trigger_kind
biomarker_context Imported condition classification; unverified.
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 1440–1452
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Prospective 15-month repeated-collection study in 22 healthy Swiss women aged 52–77 · source_derived_draft · unverified_draft
### iod-clin-urine-precision The study estimated that 10 spot or 24-hour collections were needed to estimate individual iodine status with 20% precision in these women. Condition category: biomarker_context nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The precision calculation required repeated samples, not a single diagnostic urine value. organism: Homo sapiens tissue_or_cell_type: Spot and24-hour urine experimental_model: Prospective 15-month repeated-collection study in 22 healthy Swiss women aged 52–77 limitations: The sample-number estimate is specific to this population, sampling method and 20% precision target. It is not a universal instruction to collect ten specimens or a validated single-person diagnostic cutoff. exposure: 341 24-hour urine collections and 177 corresponding fasting second-void morning spot samples; within-person variability used for precision estimates. cross_nutrient: false evidence_location: Primary indexed abstract. [iod-clin-konig2011] Ten repeat collections for urinary iodine from spot samples or 24-hour samples are needed to reliably estimate individual iodine status in women. (2011). https://pubmed.ncbi.nlm.nih.gov/21918061/ DOI: 10.3945/jn.111.144071
Complete structured claim and evidence
All iodide-supplemented groups had significant increases in TSH and median urinary iodine relative to placebo after four weeks (P<0.05).
Iodine → Serum TSH concentration source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
evidence_location
Primary indexed abstract.
experimental_model
Four-week randomized double-blind placebo-controlled dose trial in 256 euthyroid Chinese adults
exposure
Twelve groups received 0–2000 micrograms/day supplemental iodine. Mean reported dietary and salt iodine contributions were 105 ± 25 and 258 ± 101 micrograms/day.
limitations
Short study with small dose groups. Total background iodine differs among participants; the approximately 800 micrograms/day total at the 400-microgram supplement is the authors’ estimate, not a universal safe/unsafe threshold. Exact chemical formulation not verified from abstract. Baseline participants were euthyroid; increased TSH alone does not identify the molecular inhibition step.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Homo sapiens
plain_language
More iodine raised TSH in this short dose-ranging trial.
primary_references
[iod-clin-sang2012] Exploration of the safe upper level of iodine intake in euthyroid Chinese adults: a randomized double-blind trial. (2012). https://pubmed.ncbi.nlm.nih.gov/22205314/ DOI: 10.3945/ajcn.111.028001
tissue_or_cell_type
Serum thyroid indices, ultrasound and urinary iodine
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 1454–1466
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Four-week randomized double-blind placebo-controlled dose trial in 256 euthyroid Chinese adults · source_derived_draft · unverified_draft
### iod-clin-excess-tsh All iodide-supplemented groups had significant increases in TSH and median urinary iodine relative to placebo after four weeks (P<0.05). Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: More iodine raised TSH in this short dose-ranging trial. organism: Homo sapiens tissue_or_cell_type: Serum thyroid indices, ultrasound and urinary iodine experimental_model: Four-week randomized double-blind placebo-controlled dose trial in 256 euthyroid Chinese adults limitations: Short study with small dose groups. Total background iodine differs among participants; the approximately 800 micrograms/day total at the 400-microgram supplement is the authors’ estimate, not a universal safe/unsafe threshold. Exact chemical formulation not verified from abstract. Baseline participants were euthyroid; increased TSH alone does not identify the molecular inhibition step. exposure: Twelve groups received 0–2000 micrograms/day supplemental iodine. Mean reported dietary and salt iodine contributions were 105 ± 25 and 258 ± 101 micrograms/day. cross_nutrient: false evidence_location: Primary indexed abstract. [iod-clin-sang2012] Exploration of the safe upper level of iodine intake in euthyroid Chinese adults: a randomized double-blind trial. (2012). https://pubmed.ncbi.nlm.nih.gov/22205314/ DOI: 10.3945/ajcn.111.028001
Complete structured claim and evidence
Subclinical hypothyroidism occurred in 5% of the 400-microgram/day supplement group and 15–47% of the 500–2000-microgram/day groups.
Iodine → Subclinical hypothyroidism incidence source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
evidence_location
Primary indexed abstract.
experimental_model
Four-week randomized double-blind placebo-controlled dose trial in 256 euthyroid Chinese adults
exposure
Twelve groups received 0–2000 micrograms/day supplemental iodine. Mean reported dietary and salt iodine contributions were 105 ± 25 and 258 ± 101 micrograms/day.
limitations
Short study with small dose groups. Total background iodine differs among participants; the approximately 800 micrograms/day total at the 400-microgram supplement is the authors’ estimate, not a universal safe/unsafe threshold. Exact chemical formulation not verified from abstract. These percentages are reported study-group findings, not an individual risk calculator. The authors estimated about 800 micrograms/day total intake in the 400-microgram supplement group; adding two overall mean background values is not a group-specific intake measurement.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Homo sapiens
plain_language
Higher iodine exposure produced abnormal thyroid-function classifications in some participants.
primary_references
[iod-clin-sang2012] Exploration of the safe upper level of iodine intake in euthyroid Chinese adults: a randomized double-blind trial. (2012). https://pubmed.ncbi.nlm.nih.gov/22205314/ DOI: 10.3945/ajcn.111.028001
tissue_or_cell_type
Serum thyroid indices, ultrasound and urinary iodine
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 1468–1480
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Four-week randomized double-blind placebo-controlled dose trial in 256 euthyroid Chinese adults · source_derived_draft · unverified_draft
### iod-clin-excess-subclinical Subclinical hypothyroidism occurred in 5% of the 400-microgram/day supplement group and 15–47% of the 500–2000-microgram/day groups. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Higher iodine exposure produced abnormal thyroid-function classifications in some participants. organism: Homo sapiens tissue_or_cell_type: Serum thyroid indices, ultrasound and urinary iodine experimental_model: Four-week randomized double-blind placebo-controlled dose trial in 256 euthyroid Chinese adults limitations: Short study with small dose groups. Total background iodine differs among participants; the approximately 800 micrograms/day total at the 400-microgram supplement is the authors’ estimate, not a universal safe/unsafe threshold. Exact chemical formulation not verified from abstract. These percentages are reported study-group findings, not an individual risk calculator. The authors estimated about 800 micrograms/day total intake in the 400-microgram supplement group; adding two overall mean background values is not a group-specific intake measurement. exposure: Twelve groups received 0–2000 micrograms/day supplemental iodine. Mean reported dietary and salt iodine contributions were 105 ± 25 and 258 ± 101 micrograms/day. cross_nutrient: false evidence_location: Primary indexed abstract. [iod-clin-sang2012] Exploration of the safe upper level of iodine intake in euthyroid Chinese adults: a randomized double-blind trial. (2012). https://pubmed.ncbi.nlm.nih.gov/22205314/ DOI: 10.3945/ajcn.111.028001
Complete structured claim and evidence
Five-year subclinical hypothyroidism incidence was 0.2%, 2.6% and 2.9% in the regions with mildly deficient, more-than-adequate and excessive iodine exposure, respectively.
Iodine → Subclinical hypothyroidism incidence source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
evidence_location
Primary indexed abstract.
experimental_model
Prospective five-year observational follow-up in three Chinese regions;3761 enrolled and 3018 followed
exposure
Regional baseline median urinary iodine 84, 243 and 651 micrograms/L; followed 1999–2004.
limitations
Regional exposure is not randomized individual dosing; confounding and baseline susceptibility may contribute. Median urinary iodine defines cohort exposure, not an individual disease threshold. The corresponding overt hypothyroidism incidences were 0.2%, 0.5% and 0.3%, so the study does not show a monotonic rise for every thyroid outcome.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Homo sapiens
plain_language
Higher regional iodine exposure was associated with more subclinical hypothyroidism.
primary_references
[iod-clin-teng2006] Effect of iodine intake on thyroid diseases in China. (2006). https://pubmed.ncbi.nlm.nih.gov/16807415/ DOI: 10.1056/nejmoa054022
tissue_or_cell_type
Serum thyroid function/antibodies and thyroid ultrasound
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 1482–1494
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Prospective five-year observational follow-up in three Chinese regions;3761 enrolled and 3018 followed · source_derived_draft · unverified_draft
### iod-clin-regional-subclinical Five-year subclinical hypothyroidism incidence was 0.2%, 2.6% and 2.9% in the regions with mildly deficient, more-than-adequate and excessive iodine exposure, respectively. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Higher regional iodine exposure was associated with more subclinical hypothyroidism. organism: Homo sapiens tissue_or_cell_type: Serum thyroid function/antibodies and thyroid ultrasound experimental_model: Prospective five-year observational follow-up in three Chinese regions;3761 enrolled and 3018 followed limitations: Regional exposure is not randomized individual dosing; confounding and baseline susceptibility may contribute. Median urinary iodine defines cohort exposure, not an individual disease threshold. The corresponding overt hypothyroidism incidences were 0.2%, 0.5% and 0.3%, so the study does not show a monotonic rise for every thyroid outcome. exposure: Regional baseline median urinary iodine 84, 243 and 651 micrograms/L; followed 1999–2004. cross_nutrient: false evidence_location: Primary indexed abstract. [iod-clin-teng2006] Effect of iodine intake on thyroid diseases in China. (2006). https://pubmed.ncbi.nlm.nih.gov/16807415/ DOI: 10.1056/nejmoa054022
Complete structured claim and evidence
Five-year autoimmune thyroiditis incidence was 0.2%, 1.0% and 1.3% across the three increasing regional iodine-exposure categories.
Iodine → Autoimmune thyroiditis incidence source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
evidence_location
Primary indexed abstract.
experimental_model
Prospective five-year observational follow-up in three Chinese regions;3761 enrolled and 3018 followed
exposure
Regional baseline median urinary iodine 84, 243 and 651 micrograms/L; followed 1999–2004.
limitations
Regional exposure is not randomized individual dosing; confounding and baseline susceptibility may contribute. Median urinary iodine defines cohort exposure, not an individual disease threshold. Association does not establish the immune mechanism or show that every person with antibodies responds identically to iodine.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Homo sapiens
plain_language
The same cohort also found more autoimmune thyroiditis in the higher-exposure regions.
primary_references
[iod-clin-teng2006] Effect of iodine intake on thyroid diseases in China. (2006). https://pubmed.ncbi.nlm.nih.gov/16807415/ DOI: 10.1056/nejmoa054022
tissue_or_cell_type
Serum thyroid function/antibodies and thyroid ultrasound
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 1496–1508
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Prospective five-year observational follow-up in three Chinese regions;3761 enrolled and 3018 followed · source_derived_draft · unverified_draft
### iod-clin-regional-autoimmunity Five-year autoimmune thyroiditis incidence was 0.2%, 1.0% and 1.3% across the three increasing regional iodine-exposure categories. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The same cohort also found more autoimmune thyroiditis in the higher-exposure regions. organism: Homo sapiens tissue_or_cell_type: Serum thyroid function/antibodies and thyroid ultrasound experimental_model: Prospective five-year observational follow-up in three Chinese regions;3761 enrolled and 3018 followed limitations: Regional exposure is not randomized individual dosing; confounding and baseline susceptibility may contribute. Median urinary iodine defines cohort exposure, not an individual disease threshold. Association does not establish the immune mechanism or show that every person with antibodies responds identically to iodine. exposure: Regional baseline median urinary iodine 84, 243 and 651 micrograms/L; followed 1999–2004. cross_nutrient: false evidence_location: Primary indexed abstract. [iod-clin-teng2006] Effect of iodine intake on thyroid diseases in China. (2006). https://pubmed.ncbi.nlm.nih.gov/16807415/ DOI: 10.1056/nejmoa054022
Complete structured claim and evidence
After iodization, standardized thyrotoxicosis incidence initially rose 39% in the previously moderately deficient cohort and 52% in the mildly deficient cohort, peaking in 2000–2001 and 2004–2005 respectively.
Iodized salt preparation → Overt biochemical thyrotoxicosis incidence source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
evidence_location
Primary indexed abstract.
experimental_model
Twenty-one-year prospective population-register study in two open Danish cohorts, initially 533969 residents
exposure
Mandatory salt iodization at 13 ppm from mid 2000; western cohort previously moderately deficient and eastern mildly deficient; eastern follow-up only through 2008, western through 2017.
limitations
Population trend rather than randomized individual causation; age composition, diagnostic testing and prior thyroid autonomy can influence rates. Early rise and later fall are successive phases, not competing claims.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Homo sapiens
plain_language
Thyrotoxicosis increased during the early years after iodine supply changed.
primary_references
[iod-clin-denmark2018] Thyrotoxicosis after iodine fortification. A 21-year Danish population-based study. (2018). https://pubmed.ncbi.nlm.nih.gov/29851122/ DOI: 10.1111/cen.13751
tissue_or_cell_type
Incident overt biochemical thyrotoxicosis identified from thyroid tests
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 1510–1522
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Twenty-one-year prospective population-register study in two open Danish cohorts, initially 533969 residents · source_derived_draft · unverified_draft
### iod-clin-danish-early-rise After iodization, standardized thyrotoxicosis incidence initially rose 39% in the previously moderately deficient cohort and 52% in the mildly deficient cohort, peaking in 2000–2001 and 2004–2005 respectively. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Thyrotoxicosis increased during the early years after iodine supply changed. organism: Homo sapiens tissue_or_cell_type: Incident overt biochemical thyrotoxicosis identified from thyroid tests experimental_model: Twenty-one-year prospective population-register study in two open Danish cohorts, initially 533969 residents limitations: Population trend rather than randomized individual causation; age composition, diagnostic testing and prior thyroid autonomy can influence rates. Early rise and later fall are successive phases, not competing claims. exposure: Mandatory salt iodization at 13 ppm from mid 2000; western cohort previously moderately deficient and eastern mildly deficient; eastern follow-up only through 2008, western through 2017. cross_nutrient: false evidence_location: Primary indexed abstract. [iod-clin-denmark2018] Thyrotoxicosis after iodine fortification. A 21-year Danish population-based study. (2018). https://pubmed.ncbi.nlm.nih.gov/29851122/ DOI: 10.1111/cen.13751
Complete structured claim and evidence
Incidence returned to baseline or below by 2008; in the western, previously moderately deficient cohort it was 33% below baseline in 2016–2017.
Iodized salt preparation → Overt biochemical thyrotoxicosis incidence source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
evidence_location
Primary indexed abstract.
experimental_model
Twenty-one-year prospective population-register study in two open Danish cohorts, initially 533969 residents
exposure
Mandatory salt iodization at 13 ppm from mid 2000; western cohort previously moderately deficient and eastern mildly deficient; eastern follow-up only through 2008, western through 2017.
limitations
Population trend rather than randomized individual causation; age composition, diagnostic testing and prior thyroid autonomy can influence rates. Early rise and later fall are successive phases, not competing claims. Only the western cohort continued to 2017. The decline was strongest among older people; this is not a claim that every thyroid outcome improved.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Homo sapiens
plain_language
The later population pattern differed from the early rise.
primary_references
[iod-clin-denmark2018] Thyrotoxicosis after iodine fortification. A 21-year Danish population-based study. (2018). https://pubmed.ncbi.nlm.nih.gov/29851122/ DOI: 10.1111/cen.13751
tissue_or_cell_type
Incident overt biochemical thyrotoxicosis identified from thyroid tests
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 1524–1536
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Twenty-one-year prospective population-register study in two open Danish cohorts, initially 533969 residents · source_derived_draft · unverified_draft
### iod-clin-danish-late-decline Incidence returned to baseline or below by 2008; in the western, previously moderately deficient cohort it was 33% below baseline in 2016–2017. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The later population pattern differed from the early rise. organism: Homo sapiens tissue_or_cell_type: Incident overt biochemical thyrotoxicosis identified from thyroid tests experimental_model: Twenty-one-year prospective population-register study in two open Danish cohorts, initially 533969 residents limitations: Population trend rather than randomized individual causation; age composition, diagnostic testing and prior thyroid autonomy can influence rates. Early rise and later fall are successive phases, not competing claims. Only the western cohort continued to 2017. The decline was strongest among older people; this is not a claim that every thyroid outcome improved. exposure: Mandatory salt iodization at 13 ppm from mid 2000; western cohort previously moderately deficient and eastern mildly deficient; eastern follow-up only through 2008, western through 2017. cross_nutrient: false evidence_location: Primary indexed abstract. [iod-clin-denmark2018] Thyrotoxicosis after iodine fortification. A 21-year Danish population-based study. (2018). https://pubmed.ncbi.nlm.nih.gov/29851122/ DOI: 10.1111/cen.13751
Complete structured claim and evidence
Breast-milk iodine concentration was higher with maternal supplementation than with direct infant supplementation over follow-up (P<0.0001).
Iodized oil preparation → Breast-milk iodine concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
false
evidence_location
Primary PDF Methods, trial profile, Results and Table2, pp.197–209.
experimental_model
Double-blind randomized trial in Morocco;241 mother–infant pairs enrolled, 239 randomized after two age exclusions
exposure
Term infants ≤ 8 weeks; indirect arm 121 pairs: mother 400 mg iodine as oral iodized poppyseed oil, infant placebo; direct arm 118 pairs: infant about 100 mg iodine from half a 200 mg oil capsule, mother placebo; follow-up 3, 6, 9 months.
limitations
Both arms received active iodine somewhere in the pair; there was no wholly untreated arm. Breastfeeding and baseline deficiency contextualize the result; measured iodine status is not a child cognitive outcome. Actual infant study dose was about 100 mg, not the 200 mg guideline discussed elsewhere in the paper.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Homo sapiens
plain_language
Treating the mother increased the iodine delivered in her milk in this deficient setting.
primary_references
[iod-clin-bouhouch2014] Direct iodine supplementation of infants versus supplementation of their breastfeeding mothers: a double-blind, randomised, placebo-controlled trial. (2014). https://pubmed.ncbi.nlm.nih.gov/24622750/ DOI: 10.1016/s2213-8587(13)70155-4
tissue_or_cell_type
Breast milk, infant urine and thyroid function
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 1538–1550
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind randomized trial in Morocco;241 mother–infant pairs enrolled, 239 randomized after two age exclusions · source_derived_draft · unverified_draft
### iod-clin-lactation-milk Breast-milk iodine concentration was higher with maternal supplementation than with direct infant supplementation over follow-up (P<0.0001). Condition category: nutrient_deficiency nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Treating the mother increased the iodine delivered in her milk in this deficient setting. organism: Homo sapiens tissue_or_cell_type: Breast milk, infant urine and thyroid function experimental_model: Double-blind randomized trial in Morocco;241 mother–infant pairs enrolled, 239 randomized after two age exclusions limitations: Both arms received active iodine somewhere in the pair; there was no wholly untreated arm. Breastfeeding and baseline deficiency contextualize the result; measured iodine status is not a child cognitive outcome. Actual infant study dose was about 100 mg, not the 200 mg guideline discussed elsewhere in the paper. exposure: Term infants ≤ 8 weeks; indirect arm 121 pairs: mother 400 mg iodine as oral iodized poppyseed oil, infant placebo; direct arm 118 pairs: infant about 100 mg iodine from half a 200 mg oil capsule, mother placebo; follow-up 3, 6, 9 months. cross_nutrient: false evidence_location: Primary PDF Methods, trial profile, Results and Table2, pp.197–209. [iod-clin-bouhouch2014] Direct iodine supplementation of infants versus supplementation of their breastfeeding mothers: a double-blind, randomised, placebo-controlled trial. (2014). https://pubmed.ncbi.nlm.nih.gov/24622750/ DOI: 10.1016/s2213-8587(13)70155-4
Complete structured claim and evidence
Infant urinary iodine was higher in the maternal-supplement arm (P=0.042); group medians exceeded 100 micrograms/L at 3 and 6 months in that arm, versus only 6 months in the direct-infant arm.
Iodized oil preparation → Urinary iodine concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
false
evidence_location
Primary PDF Methods, trial profile, Results and Table2, pp.197–209.
experimental_model
Double-blind randomized trial in Morocco;241 mother–infant pairs enrolled, 239 randomized after two age exclusions
exposure
Term infants ≤ 8 weeks; indirect arm 121 pairs: mother 400 mg iodine as oral iodized poppyseed oil, infant placebo; direct arm 118 pairs: infant about 100 mg iodine from half a 200 mg oil capsule, mother placebo; follow-up 3, 6, 9 months.
limitations
Both arms received active iodine somewhere in the pair; there was no wholly untreated arm. Breastfeeding and baseline deficiency contextualize the result; measured iodine status is not a child cognitive outcome. Actual infant study dose was about 100 mg, not the 200 mg guideline discussed elsewhere in the paper. The 100-microgram/L statement concerns group medians as interpreted by the paper, not proof of adequacy in every infant.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Homo sapiens
plain_language
The maternal route improved the infants’ measured iodine status for longer.
primary_references
[iod-clin-bouhouch2014] Direct iodine supplementation of infants versus supplementation of their breastfeeding mothers: a double-blind, randomised, placebo-controlled trial. (2014). https://pubmed.ncbi.nlm.nih.gov/24622750/ DOI: 10.1016/s2213-8587(13)70155-4
tissue_or_cell_type
Breast milk, infant urine and thyroid function
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 1552–1564
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind randomized trial in Morocco;241 mother–infant pairs enrolled, 239 randomized after two age exclusions · source_derived_draft · unverified_draft
### iod-clin-lactation-infant-urine Infant urinary iodine was higher in the maternal-supplement arm (P=0.042); group medians exceeded 100 micrograms/L at 3 and 6 months in that arm, versus only 6 months in the direct-infant arm. Condition category: nutrient_deficiency nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The maternal route improved the infants’ measured iodine status for longer. organism: Homo sapiens tissue_or_cell_type: Breast milk, infant urine and thyroid function experimental_model: Double-blind randomized trial in Morocco;241 mother–infant pairs enrolled, 239 randomized after two age exclusions limitations: Both arms received active iodine somewhere in the pair; there was no wholly untreated arm. Breastfeeding and baseline deficiency contextualize the result; measured iodine status is not a child cognitive outcome. Actual infant study dose was about 100 mg, not the 200 mg guideline discussed elsewhere in the paper. The 100-microgram/L statement concerns group medians as interpreted by the paper, not proof of adequacy in every infant. exposure: Term infants ≤ 8 weeks; indirect arm 121 pairs: mother 400 mg iodine as oral iodized poppyseed oil, infant placebo; direct arm 118 pairs: infant about 100 mg iodine from half a 200 mg oil capsule, mother placebo; follow-up 3, 6, 9 months. cross_nutrient: false evidence_location: Primary PDF Methods, trial profile, Results and Table2, pp.197–209. [iod-clin-bouhouch2014] Direct iodine supplementation of infants versus supplementation of their breastfeeding mothers: a double-blind, randomised, placebo-controlled trial. (2014). https://pubmed.ncbi.nlm.nih.gov/24622750/ DOI: 10.1016/s2213-8587(13)70155-4
Complete structured claim and evidence
Infant thyroid hypofunction classifications were less frequent with indirect maternal supplementation (P=0.023), although infant TSH and T4 concentrations did not differ significantly between groups over time (P=0.597 and 0.184).
Iodized oil preparation → Infant thyroid hypofunction classification source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
false
evidence_location
Primary PDF Methods, trial profile, Results and Table2, pp.197–209.
experimental_model
Double-blind randomized trial in Morocco;241 mother–infant pairs enrolled, 239 randomized after two age exclusions
exposure
Term infants ≤ 8 weeks; indirect arm 121 pairs: mother 400 mg iodine as oral iodized poppyseed oil, infant placebo; direct arm 118 pairs: infant about 100 mg iodine from half a 200 mg oil capsule, mother placebo; follow-up 3, 6, 9 months.
limitations
Both arms received active iodine somewhere in the pair; there was no wholly untreated arm. Breastfeeding and baseline deficiency contextualize the result; measured iodine status is not a child cognitive outcome. Actual infant study dose was about 100 mg, not the 200 mg guideline discussed elsewhere in the paper. No serious adverse events were reported; this does not establish safety for other infant doses, preparations or settings.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Homo sapiens
plain_language
A categorical thyroid outcome improved even though average hormone comparisons were not significant.
primary_references
[iod-clin-bouhouch2014] Direct iodine supplementation of infants versus supplementation of their breastfeeding mothers: a double-blind, randomised, placebo-controlled trial. (2014). https://pubmed.ncbi.nlm.nih.gov/24622750/ DOI: 10.1016/s2213-8587(13)70155-4
tissue_or_cell_type
Breast milk, infant urine and thyroid function
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 1566–1578
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind randomized trial in Morocco;241 mother–infant pairs enrolled, 239 randomized after two age exclusions · source_derived_draft · unverified_draft
### iod-clin-lactation-hypofunction Infant thyroid hypofunction classifications were less frequent with indirect maternal supplementation (P=0.023), although infant TSH and T4 concentrations did not differ significantly between groups over time (P=0.597 and 0.184). Condition category: nutrient_deficiency nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A categorical thyroid outcome improved even though average hormone comparisons were not significant. organism: Homo sapiens tissue_or_cell_type: Breast milk, infant urine and thyroid function experimental_model: Double-blind randomized trial in Morocco;241 mother–infant pairs enrolled, 239 randomized after two age exclusions limitations: Both arms received active iodine somewhere in the pair; there was no wholly untreated arm. Breastfeeding and baseline deficiency contextualize the result; measured iodine status is not a child cognitive outcome. Actual infant study dose was about 100 mg, not the 200 mg guideline discussed elsewhere in the paper. No serious adverse events were reported; this does not establish safety for other infant doses, preparations or settings. exposure: Term infants ≤ 8 weeks; indirect arm 121 pairs: mother 400 mg iodine as oral iodized poppyseed oil, infant placebo; direct arm 118 pairs: infant about 100 mg iodine from half a 200 mg oil capsule, mother placebo; follow-up 3, 6, 9 months. cross_nutrient: false evidence_location: Primary PDF Methods, trial profile, Results and Table2, pp.197–209. [iod-clin-bouhouch2014] Direct iodine supplementation of infants versus supplementation of their breastfeeding mothers: a double-blind, randomised, placebo-controlled trial. (2014). https://pubmed.ncbi.nlm.nih.gov/24622750/ DOI: 10.1016/s2213-8587(13)70155-4
Complete structured claim and evidence
Median dried-blood-spot thyroglobulin fell from 49 to 13 and 8 micrograms/L at 5 and 10 months after iodized salt introduction; proportions above 40 micrograms/L fell from over two thirds to 7% and 3%.
Iodized salt preparation → Dried-blood-spot thyroglobulin concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
cross_nutrient
false
evidence_location
Primary indexed abstract.
experimental_model
Assay-standardization study in 700 iodine-sufficient euthyroid anti-Tg-antibody-negative children aged 5–14 and separate 10-month iodized-salt intervention
exposure
International reference sample and longitudinal measurements before, 5 months and 10 months after salt iodization in deficient children.
limitations
Assay-specific pediatric reference distribution; not a universal adult/pregnancy threshold. Anti-Tg-antibody-positive children were excluded from the reference sample; antibody interference and other thyroid diseases remain relevant.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Homo sapiens
plain_language
This thyroglobulin assay tracked the population’s response to iodine repletion.
primary_references
[iod-clin-tg2006] Assessment of iodine status using dried blood spot thyroglobulin: development of reference material and establishment of an international reference range in iodine-sufficient children. (2006). https://pubmed.ncbi.nlm.nih.gov/16968789/ DOI: 10.1210/jc.2006-1370
tissue_or_cell_type
Dried whole-blood thyroglobulin assay
trigger_kind
biomarker_context Imported condition classification; unverified.
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 1580–1592
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Assay-standardization study in 700 iodine-sufficient euthyroid anti-Tg-antibody-negative children aged 5–14 and separate 10-month iodized-salt intervention · source_derived_draft · unverified_draft
### iod-clin-dbs-tg-response Median dried-blood-spot thyroglobulin fell from 49 to 13 and 8 micrograms/L at 5 and 10 months after iodized salt introduction; proportions above 40 micrograms/L fell from over two thirds to 7% and 3%. Condition category: biomarker_context nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: This thyroglobulin assay tracked the population’s response to iodine repletion. organism: Homo sapiens tissue_or_cell_type: Dried whole-blood thyroglobulin assay experimental_model: Assay-standardization study in 700 iodine-sufficient euthyroid anti-Tg-antibody-negative children aged 5–14 and separate 10-month iodized-salt intervention limitations: Assay-specific pediatric reference distribution; not a universal adult/pregnancy threshold. Anti-Tg-antibody-positive children were excluded from the reference sample; antibody interference and other thyroid diseases remain relevant. exposure: International reference sample and longitudinal measurements before, 5 months and 10 months after salt iodization in deficient children. cross_nutrient: false evidence_location: Primary indexed abstract. [iod-clin-tg2006] Assessment of iodine status using dried blood spot thyroglobulin: development of reference material and establishment of an international reference range in iodine-sufficient children. (2006). https://pubmed.ncbi.nlm.nih.gov/16968789/ DOI: 10.1210/jc.2006-1370
Complete structured claim and evidence
The third and 97th percentiles of the standardized dried-blood-spot Tg assay were 4 and 40 micrograms/L in the 700 iodine-sufficient, euthyroid, anti-Tg-negative children.
Dried-blood-spot thyroglobulin concentration → Human thyroglobulin source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
cross_nutrient
false
evidence_location
Primary indexed abstract.
experimental_model
Assay-standardization study in 700 iodine-sufficient euthyroid anti-Tg-antibody-negative children aged 5–14 and separate 10-month iodized-salt intervention
exposure
International reference sample and longitudinal measurements before, 5 months and 10 months after salt iodization in deficient children.
limitations
Assay-specific pediatric reference distribution; not a universal adult/pregnancy threshold. Anti-Tg-antibody-positive children were excluded from the reference sample; antibody interference and other thyroid diseases remain relevant.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Homo sapiens
plain_language
The study established a reference distribution for a particular pediatric assay.
primary_references
[iod-clin-tg2006] Assessment of iodine status using dried blood spot thyroglobulin: development of reference material and establishment of an international reference range in iodine-sufficient children. (2006). https://pubmed.ncbi.nlm.nih.gov/16968789/ DOI: 10.1210/jc.2006-1370
tissue_or_cell_type
Dried whole-blood thyroglobulin assay
trigger_kind
biomarker_context Imported condition classification; unverified.
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 1594–1606
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Assay-standardization study in 700 iodine-sufficient euthyroid anti-Tg-antibody-negative children aged 5–14 and separate 10-month iodized-salt intervention · source_derived_draft · unverified_draft
### iod-clin-dbs-tg-reference The third and 97th percentiles of the standardized dried-blood-spot Tg assay were 4 and 40 micrograms/L in the 700 iodine-sufficient, euthyroid, anti-Tg-negative children. Condition category: biomarker_context nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The study established a reference distribution for a particular pediatric assay. organism: Homo sapiens tissue_or_cell_type: Dried whole-blood thyroglobulin assay experimental_model: Assay-standardization study in 700 iodine-sufficient euthyroid anti-Tg-antibody-negative children aged 5–14 and separate 10-month iodized-salt intervention limitations: Assay-specific pediatric reference distribution; not a universal adult/pregnancy threshold. Anti-Tg-antibody-positive children were excluded from the reference sample; antibody interference and other thyroid diseases remain relevant. exposure: International reference sample and longitudinal measurements before, 5 months and 10 months after salt iodization in deficient children. cross_nutrient: false evidence_location: Primary indexed abstract. [iod-clin-tg2006] Assessment of iodine status using dried blood spot thyroglobulin: development of reference material and establishment of an international reference range in iodine-sufficient children. (2006). https://pubmed.ncbi.nlm.nih.gov/16968789/ DOI: 10.1210/jc.2006-1370
Complete structured claim and evidence

Availability and dependencies

Each situation shows the normal role first, then what the sources report under a specific condition. A shortfall in the diet, a fault in the machinery, and a low blood reading are kept separate because they are not the same thing.

AP-1-dependent NIS sorting impairment

Condition: machinery_impairment · Experimental depletion of AP-1 adaptor subunits in MDCK cells expressing human NIS

Normal role: Membrane-localized transport machinery controls availability of iodide for thyroid hormone synthesis.

Recorded consequence: NIS is missorted or less efficiently delivered to the cell surface.

Scope: Cellular trafficking perturbations, not an established human dietary deficiency syndrome.

NIS T354P iodide transport defect

Condition: machinery_impairment · Homozygous human NIS T354P variant

Normal role: Membrane-localized transport machinery controls availability of iodide for thyroid hormone synthesis.

Recorded consequence: Reduced iodide accumulation capacity

Scope: Patient observation plus COS-7 functional expression

SLC26A7 Q500Ter machinery defect

Condition: machinery_impairment · Homozygous c.1498C>T / p.Gln500Ter truncation

Normal role: Membrane-localized transport machinery controls availability of iodide for thyroid hormone synthesis.

Recorded consequence: Abnormal membrane localization and loss of measured iodide conductance

Scope: Two siblings plus expression-cell functional tests

Truncating SLC26A7-associated congenital hypothyroidism

Condition: machinery_impairment · Homozygous truncating SLC26A7 variants

Normal role: Membrane-localized transport machinery controls availability of iodide for thyroid hormone synthesis.

Recorded consequence: Goitrous congenital hypothyroidism

Scope: Six human families; 13 affected individuals

DUOX2 truncating machinery defects

Condition: machinery_impairment · Inherited truncating DUOX2 alleles in a selected nine-patient series

Normal role: DUOX2 supplies peroxide for iodide organification.

Recorded consequence: Partial or complete organification failure

Scope: One homozygous severe permanent case; three heterozygous transient cases

DUOXA2 Y246X machinery impairment

Condition: machinery_impairment · Biallelic DUOXA2 p.Y246X

Normal role: DUOXA2 supports functional DUOX2.

Recorded consequence: Loss of reconstituted DUOX2 activity and congenital hypothyroidism

Scope: Human homozygous proband and reconstitution

Inherited iodotyrosine recycling defects

Condition: machinery_impairment · IYD variants identified in four patients from three families

Normal role: IYD recovers iodide from iodotyrosines.

Recorded consequence: Low enzyme activity and severe goitrous hypothyroidism in infancy or childhood

Scope: Selected human genetic cases

MCT8 transport failure despite retained hormone binding

Condition: machinery_impairment · Patient-derived D424N substitution, numbered D498N in the long MCT8 isoform.

Normal role: MCT8 binds hormone and changes conformation to move it across the membrane.

Recorded consequence: T4 binding persists while transport is strongly impaired.

Scope: Purified human mutant and transfected cells.

Engineered OATP1C1 recognition defect

Condition: machinery_impairment · K376A substitution in the human transporter.

Normal role: OATP1C1 transports T4.

Recorded consequence: Radiolabeled T4 uptake was abolished despite preserved surface abundance.

Scope: Engineered HEK293 model.

Combined mouse brain hormone transporter loss

Condition: machinery_impairment · Global loss of both mouse transporters.

Normal role: Mct8 and Oatp1c1 contribute to brain T4 entry.

Recorded consequence: Severe brain hormone depletion persists despite increased D2 activity.

Scope: Mouse double knockout compared with single mutants and wild type.

Dio2 loss alters T4 feedback

Condition: machinery_impairment · Targeted mouse Dio2 deletion.

Normal role: Local T4 conversion contributes to TSH feedback suppression.

Recorded consequence: T4 fails to suppress TSH under tested hypothyroid conditions; T3 remains effective.

Scope: Mouse knockout hormone challenge.

SECISBP2-dependent deiodination defect

Condition: machinery_impairment · Recessive SECISBP2 mutations in the studied families.

Normal role: SECISBP2 supports selenocysteine incorporation during selenoprotein translation.

Recorded consequence: Patient fibroblasts showed reduced DIO2 enzymatic activity.

Scope: Three affected siblings and an unrelated child; genetic and cellular study.

Reduced DIO2 turnover after WSB1 knockdown

Condition: machinery_impairment · WSB1 RNA interference in transfected HEK293 cells.

Normal role: WSB1 contributes to DIO2 ubiquitination and turnover.

Recorded consequence: D2 steady-state level rises and its lifetime is prolonged.

Scope: Human cultured cells expressing DIO2 constructs.

Iodine repletion restored thyroid hormone status in these moderately deficient children.

Condition: nutrient_deficiency · Moderate iodine deficiency with frequent goiter and low T4. Same moderately deficient schoolchildren.

Normal role: Iodine supplies atoms for thyroid hormone production; circulating hormone values and clinical outcomes are distinct endpoints.

Recorded consequence: At 24 weeks, mean total T4 in iodine-treated children was approximately 40% higher than baseline and hypothyroxinemia prevalence was below 1%; corresponding placebo-group status did not improve significantly. Iodine treatment improved rapid target marking performance compared with placebo at 24 weeks (reported adjusted P<0.0001). Iodine treatment improved symbol search performance compared with placebo at 24 weeks (reported adjusted P<0.0001). Iodine treatment improved rapid object naming performance compared with placebo at 24 weeks (reported adjusted P<0.0001). Iodine treatment improved Raven’s Coloured Progressive Matrices performance compared with placebo at 24 weeks (reported adjusted P<0.0001).

Scope: Randomized double-blind placebo-controlled 24-week trial in 310 moderately iodine-deficient Albanian children aged 10–12; One supervised oral dose of iodized poppyseed oil containing 400 mg iodine versus sunflower-oil placebo; baseline median urinary iodine 43 micrograms/L, 87% goitrous; iodine 159/placebo 151 randomized.

Starting iodine during this mildly deficient pregnancy trial did not significantly improve verbal IQ.

Condition: nutrient_deficiency · Mild group-level iodine deficiency/low adequacy at enrollment during early pregnancy.

Normal role: Iodine supplies atoms for thyroid hormone production; circulating hormone values and clinical outcomes are distinct endpoints.

Recorded consequence: Verbal IQ at 5–6 years averaged 89.5 versus 90.2 with maternal iodine versus placebo; reported difference −0.7 (95% CI −2.9 to 1.5), P=0.77. Performance IQ averaged 97.5 versus 99.1; reported iodine-minus-placebo difference −1.6 (95% CI −4.5 to 1.3), P=0.44. The BRIEF-P global executive score averaged 90.6 versus 91.5; reported difference −0.9 (95% CI −6.8 to 5.0), P=0.74.

Scope: Randomized double-blind placebo-controlled maternal trial in Bangkok and Bangalore; 832 women randomized, 313 children assessed for IQ and 315 for executive function at age 5–6; 200 micrograms iodine/day as potassium iodide until delivery; mean enrollment 10.7 weeks gestation; baseline median urinary iodine 131 micrograms/L; IQ iodine 159/placebo 154, executive function 159/156.

In severe deficiency, supplying iodine before conception prevented the study-defined definite neurological syndrome in this follow-up.

Condition: nutrient_deficiency · Severe endemic iodine deficiency before fetal development.

Normal role: Iodine supplies atoms for thyroid hormone production; circulating hormone values and clinical outcomes are distinct endpoints.

Recorded consequence: Among children conceived after maternal trial entry, the follow-up classified 0 of 237 in the iodinated-oil group and 14 of 215 in the saline group as definite cases of the historical neurological iodine-deficiency syndrome.

Scope: Historical double-blind controlled maternal iodinated-oil trial begun 1966, with children born 1966–1972 followed through 1982 in five selected Papua New Guinea villages; Intramuscular iodinated oil versus saline; comparison by conception before/after maternal trial entry. The follow-up paper does not verify the injection dose in the inspected methods.

One urine result can vary substantially within the same person.

Condition: biomarker_context · Interpreting repeated urine measurements as individual status. Same repeated-collection precision analysis.

Normal role: Urinary iodine reflects recent intake and excretion rather than a direct thyroid or brain iodine inventory. Measurements require a defined time window and precision target.

Recorded consequence: Mean within-person variability was 32% for measured 24-hour iodine excretion, 33% for estimated 24-hour excretion and 38% for spot urinary iodine concentration. The study estimated that 10 spot or 24-hour collections were needed to estimate individual iodine status with 20% precision in these women.

Scope: Prospective 15-month repeated-collection study in 22 healthy Swiss women aged 52–77; 341 24-hour urine collections and 177 corresponding fasting second-void morning spot samples; within-person variability used for precision estimates.

Treating the mother increased the iodine delivered in her milk in this deficient setting.

Condition: nutrient_deficiency · Maternal and infant iodine deficiency without effective salt iodization. Same deficient breastfeeding mother–infant pairs. Same mother–infant trial.

Normal role: Breast milk is an iodine supply route for breastfed infants. Urinary iodine is an exposure/status marker, not a direct developmental test. Iodine supply supports infant thyroid function; categorical and continuous endpoints differ.

Recorded consequence: Breast-milk iodine concentration was higher with maternal supplementation than with direct infant supplementation over follow-up (P<0.0001). Infant urinary iodine was higher in the maternal-supplement arm (P=0.042); group medians exceeded 100 micrograms/L at 3 and 6 months in that arm, versus only 6 months in the direct-infant arm. Infant thyroid hypofunction classifications were less frequent with indirect maternal supplementation (P=0.023), although infant TSH and T4 concentrations did not differ significantly between groups over time (P=0.597 and 0.184).

Scope: Double-blind randomized trial in Morocco;241 mother–infant pairs enrolled, 239 randomized after two age exclusions; Term infants ≤ 8 weeks; indirect arm 121 pairs: mother 400 mg iodine as oral iodized poppyseed oil, infant placebo; direct arm 118 pairs: infant about 100 mg iodine from half a 200 mg oil capsule, mother placebo; follow-up 3, 6, 9 months.

This thyroglobulin assay tracked the population’s response to iodine repletion.

Condition: biomarker_context · Interpretation of thyroid-stimulation markers during repletion.

Normal role: Thyroglobulin concentration can reflect thyroid stimulation but does not directly measure dietary intake or hormone synthesis rate.

Recorded consequence: Median dried-blood-spot thyroglobulin fell from 49 to 13 and 8 micrograms/L at 5 and 10 months after iodized salt introduction; proportions above 40 micrograms/L fell from over two thirds to 7% and 3%.

Scope: Assay-standardization study in 700 iodine-sufficient euthyroid anti-Tg-antibody-negative children aged 5–14 and separate 10-month iodized-salt intervention; International reference sample and longitudinal measurements before, 5 months and 10 months after salt iodization in deficient children.

The study established a reference distribution for a particular pediatric assay.

Condition: biomarker_context · Applying a reference distribution outside or within its validated sample.

Normal role: Assay reference values describe a selected population and method.

Recorded consequence: The third and 97th percentiles of the standardized dried-blood-spot Tg assay were 4 and 40 micrograms/L in the 700 iodine-sufficient, euthyroid, anti-Tg-negative children.

The sources

Every document behind this chapter is preserved word for word. Open one to read it in full with its recorded conflicts marked in place.

Calcium: mechanism-first literature curation (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Iodine addendum: iodide excess and cellular export (2026-09-18)Calil-Silveira et al. (2016). Iodide excess regulates its own efflux: a possible involvement of pendrin. DOI: 10.1152/ajpcell.00210.2015. https://pubmed.ncbi.nlm.nih.gov/26791486/ · unverified_draftRead preserved source
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Selenium: literature corrections and mechanism additionsMetabolic Ledger literature curation, 17 September 2026; primary papers linked individually · secondary_verifiedRead preserved source
Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source

Recorded disagreements

Where two sources say different things, both are kept and the difference is explained. You can discuss a disagreement or propose a mechanism that might account for it.

SLC26A7 thyroid membrane localization remains unsettledThe 2019 human tissue study reports predominantly apical SLC26A7, whereas the 2026 human thyrocyte study reports basolateral localization. Both are published descriptions of the human thyroid protein, beyond simply different transport assay outcomes. The 2018 negative HEK293 efflux result and 2019 positive polarized-cell result are retained as experimental context, not independently counted as a contradiction.Read the recorded disagreement

Open questions in this collection

Questions the curators could not answer from the sources in front of them, kept here with the reason each one is still open. These are gaps in this collection, not findings or proof that no one has studied them.

Which individual iodine measurement reliably distinguishes short-term intake fluctuation from sustained thyroid or brain shortage?Urine varies within a person; DBS-Tg reference values are assay- and population-specific.
Does iodine supplementation begun before conception improve child outcomes in mild deficiency?The modern selected trial began at a mean 10.7 weeks gestation, while the historical preconception trial involved severe deficiency. The settings cannot be treated as interchangeable.
Which molecular steps explain the improved iodized-salt response after iron treatment?The clinical trials measure thyroid volume and hormones; they do not distinguish TPO catalysis, oxygen transport, deiodination or other iron-related effects.
What caused the selenium-associated hormone changes in severe iodine/selenium co-deficiency?DIO1 reactivation was an author-proposed explanation. Tissue deiodinase flux and symptoms were not measured in the reported intervention.
What exposure produces iodine excess in a specific individual?Background intake, prior deficiency, thyroid autonomy, immune disease and timing matter; short dose trials and regional cohort medians do not establish one universal cutoff.
Whether selenium supplementation can rescue a specific hormone-transport or SECISBP2 defect.The selected genetic and structural studies do not test such nutritional rescue.
Human equivalence of compensation seen in Mct8/Oatp1c1 mouse models.Species-specific transporter expression and developmental models prevent direct extrapolation.
Whether ordinary dietary vitamin A or iodine availability limits RXRA–THRB complex formation.The reused receptor assay studies shared machinery, not nutritional deficiency.
Clinical importance of silychristin transport inhibition at ordinary oral exposures.Micromolar cell assays and purified structures do not define in-vivo exposure or clinical outcomes.
Whether nutritional riboflavin insufficiency limits iodine repletion by impairing thyroid IYD in humans remains unestablished by these molecular studies.FMN requirement and cofactor replacement establish biochemical dependence, not a dietary threshold.
The precise inhibitory iodinated species responsible for acute block is not determined by the dog-slice experiment.Methimazole identifies an oxidation-dependent step without isolating its product.
The physiological electron donor regenerating reduced IYD-bound FMN is not identified by the selected reductive assays.Sodium dithionite is an experimental reductant.
Rat escape kinetics cannot predict every human response to excess iodine.Species, exposure route, thyroid disease and developmental stage differ.
What determines apical versus basolateral SLC26A7 localization in human thyroid, and which location controls net iodide availability?Published human localization differs; positive high-halide conductance does not resolve physiological localization or contribution.
How much of dietary iodide absorption in humans is attributable to intestinal NIS under different iodine states?The direct intestinal study here is rodent-based and does not quantify a human fractional contribution.
Do nutritional sodium or chloride insufficiency states measurably constrain iodine repletion in people?Direct ion coupling and shared transport substrates do not establish a clinical dietary gate; no clinical causal claim is made.

Chapters are assembled from supplied drafts and curated literature summaries. Statements remain unverified against the primary studies, and the ledger is not medical advice.

Evidence, AI assistance and curation standards

Iodine

The mechanisms

DIO1 converts T4 into the active thyroid hormone T3.

DIO2 converts T4 into the active thyroid hormone T3.

DIO3 lowers thyroid-hormone activity by converting T4 to reverse T3.

DIO3 lowers thyroid-hormone activity by converting T3 to 3,3-prime-T2.

RXRA complexed with TR beta and enhanced thyroid-response-element binding.

Vitamin A without iodine supplementation lowered TSH in the iodine-deficient study setting.

Thyroid volume and thyroglobulin decreased with vitamin A alone; total T4 showed no significant treatment-interaction effect.

Thyroxine adsorbed to calcium carbonate under acidic in-vitro conditions.

Simultaneous calcium carbonate reduced measured levothyroxine absorption in a seven-volunteer experiment.

Pendrin abundance increased after 24 hours at 1 mM NaI; lower tested concentrations and 48-hour total abundance showed no significant increase.

Surface pendrin increased at 24 and 48 hours by flow cytometry; immunofluorescence also detected an increase at 12 hours.

Excess iodide slowed pendrin loss during cycloheximide treatment, supporting increased protein stability.

Iodide pretreatment for 12, 24 and 48 hours increased fractional radioiodide efflux despite reduced iodide uptake.

Ano1 mRNA abundance did not significantly change after 24 hours of excess iodide.

Expression of cloned human NIS conferred perchlorate-sensitive iodide uptake on COS-7 cells.

Rat NIS expressed in Xenopus oocytes transported iodide with two sodium ions per anion and generated inward electrogenic transport.

Thermodynamic fits to rat IEC-6 NIS transport data estimated an iodide Kd of 224 micromolar without sodium binding and 22.4 micromolar in the sodium-bound state.

The iodide-bound cryo-EM structure of engineered rat NIS contained density assigned to one iodide and two sodium ions in the substrate-binding cavity.

Depletion of the AP-1B mu1B subunit in polarized MDCK cells caused expressed human NIS to be missorted toward the apical membrane while retaining transport function.

Combined loss of AP-1A and AP-1B mu1 subunits reduced trafficking of human NIS to the MDCK cell plasma membrane.

Human NIS T354P expressed in COS-7 cells showed markedly reduced iodide uptake compared with normal NIS.

NIS immunolocalization in rat small-intestinal enterocytes was restricted to their apical surface.

Rodent intestinal brush-border membrane vesicles accumulated iodide in a sodium-dependent, perchlorate-sensitive manner.

Mouse mammary Slc5a5 mRNA abundance increased during lactation.

Human thyroid immunolocalization detected pendrin at the apical membrane in a subset of follicular epithelial cells.

Human pendrin expression supported iodide efflux in COS-7 and CHO mammalian-cell transport experiments.

Expression of human pendrin increased chloride transport in Xenopus oocytes and Sf9 cells, alongside increased iodide transport.

Ishii et al. detected human thyroid SLC26A7 staining predominantly on the apical side facing the follicular lumen.

MDCK monolayers coexpressing human NIS and SLC26A7 transferred more basal-chamber radioiodide into the apical chamber after 45 minutes than monolayers expressing NIS alone.

Human SLC26A7 Q500Ter expressed in MDCK cells aggregated in the cytosol instead of showing the predominant surface localization of wild-type protein.

Human SLC26A7 Q500Ter did not produce the wild-type enhancement of iodide-dependent current and iodide-sensitive fluorescence responses in HEK293T cells.

Cangul et al. found no enhancement of radioiodide efflux from HEK293 cells coexpressing human NIS and SLC26A7 compared with control cells, whereas pendrin enhanced efflux.

Homozygous truncating SLC26A7 variants segregated with goitrous congenital hypothyroidism in six unrelated families studied by Cangul et al.

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

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

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

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

Human SLC26A7 cryo-EM maps in the iodide-loaded state supported iodide assignments at a canonical site and a second site near the gate-domain interface.

Human SLC26A7 expression in HEK293T cells generated chloride and iodide currents that increased when bath halide concentrations rose from 50 to 149 mM.

The 2026 Finnish SLC26A7 study reported basolateral SLC26A7 localization in human thyrocytes, with intense staining in hyperthyroid samples.

Human DUOXA2 coexpression permitted DUOX2 ER-to-Golgi maturation and plasma-membrane delivery in a heterologous system.

Coexpressing DUOXA2 reconstituted functional human DUOX2-dependent hydrogen-peroxide generation.

A homozygous truncating DUOX2 mutation accompanied a complete iodide-organification defect in the severe permanent case in the 2002 series.

Human DUOXA2 p.Y246X failed to reconstitute DUOX2 activity in vitro.

The homozygous DUOXA2 Y246X proband had congenital hypothyroidism with goiter and partial iodine-organification impairment.

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.

In CHO cells expressing human TPO, inhibition of heme biosynthesis by succinylacetone decreased surface TPO expression by approximately 80%.

Exposing human TPO-expressing CHO cells to 10 micromolar H2O2 for 10 minutes increased cell-surface peroxidase activity by 65%.

Cryo-EM structures of the human TPO extracellular domain resolve heme at the peroxidase active site.

Recombinant human TG produced a T4 signal after in-vitro iodination and proteolysis, whereas omission of iodide prevented the reaction.

Replacing human TG acceptors Y24, Y2573, Y2766 and Y1310 with phenylalanine eliminated detectable T4 formation in the reconstituted assay.

Replacing human TG donor residues Y2540, Y2766, Y108, Y234 and Y149 with phenylalanine suppressed significant T4 synthesis.

Human thyroid lysosomal extracts cleaved radioiodinated rabbit TG into discrete iodine-bearing peptides before iodoamino-acid release.

Combined inhibition of cathepsins B, D and L reduced long-incubation iodoamino-acid release from radioiodinated rabbit TG by 80–90%.

Purified soluble human IYD released radiolabeled iodide from diiodotyrosine during reductive enzyme assays.

Human IYD crystal structures show one bound FMN per polypeptide, with iodotyrosine contacting its isoalloxazine ring in the substrate complex.

The substrate analog 3-fluoro-L-tyrosine stabilized a one-electron-reduced FMN semiquinone during reductive titration of soluble human IYD.

Replacing FMN with 2-prime-deoxyFMN in human IYD lowered iodotyrosine dehalogenation efficiency by more than fivefold while increasing turnover number by more than sixfold.

The IYD variants identified in four affected patients showed markedly reduced iodotyrosine-deiodinase activity in vitro.

The four patients with damaging IYD variants developed severe goitrous hypothyroidism evident in infancy or childhood.

Rats given 0.05% NaI in drinking water had lower thyroid NIS mRNA and protein at both 1 and 6 days.

During continued 0.05% NaI exposure, rat serum T4 and T3 fell at day 1 but returned to normal by day 6.

Iodide inhibited stimulated H2O2 generation in dog thyroid slices, including responses to probes acting downstream of receptor activation.

Methimazole suppressed the inhibitory effects of iodide on stimulated H2O2 generation in dog thyroid slices.

Purified hog TPO catalyzed iodine incorporation into hog thyroglobulin in kinetic assays of protein iodination.

Recombinant human TPO catalyzed T4 formation from recombinant human TG in the direct TPO-versus-lactoperoxidase comparison.

Iodinating human goiter TG with hog TPO for 90 minutes produced 0.3 T3 residues per TG molecule, measured after enzymatic hydrolysis.

During TPO-catalyzed hormone formation in TG, approximately one protein-bound dehydroalanine residue was formed per hormone residue.

Rat MCT8 expression increased uptake of 10 nM radiolabeled T4 approximately tenfold in Xenopus oocytes.

Rat MCT8 expression increased uptake of 10 nM radiolabeled T3 approximately tenfold in Xenopus oocytes.

Human MCT8 structure places the T3 carboxylate against Arg371 and its iodine atoms in hydrophobic pockets; substitutions of substrate-contact residues reduce cellular T3 uptake.

Silychristin inhibited human MCT8-mediated T4 uptake in transfected HeLa cells; structural and binding experiments support trapping an outward-facing transporter state.

Human MCT8 D424N retained measurable T4 binding but had strongly impaired cellular T4 transport, showing that binding alone does not establish transport competence.

The 2.3-angstrom human OATP1C1 structure places T4 in a side pocket where K376, N399 and S562 coordinate the outer-ring hydroxyl group.

Human OATP1C1 K376A abolished measured radiolabeled-T4 uptake without lowering cell-surface expression relative to wild type.

Brain uptake of injected radiolabeled T4 was strongly reduced in Mct8/Oatp1c1 double-knockout mice; either single knockout retained roughly half the wild-type uptake.

At postnatal day 21, double-knockout forebrain T3 content was approximately 10% of wild type, whereas Oatp1c1 single-knockout forebrain T3 was preserved.

D2 activity in P21 forebrain and cerebellum rose almost tenfold in Mct8/Oatp1c1 double-knockout mice despite persistent severe brain hormone depletion.