T4

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

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

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

evidence_span

{"source_cache": "artifacts/sulforaphane-research/30735751.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0797bbf31c4a1fa8cf002b8752410e80a92e8a351c44273335bc52f19e66b2ea", "start_char": 0, "end_char": 1494, "text_sha256": "0797bbf31c4a1fa8cf002b8752410e80a92e8a351c44273335bc52f19e66b2ea"}

experimental_model

Thyroid safety analysis within a randomized beverage trial

exposure

Baseline and 84 days of glucoraphanin/sulforaphane-rich beverage

limitations

Subsample safety analysis; not all populations, iodine-deficient states, products, doses or lifelong exposure.

nutrient_topic

Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. · Sulforaphane / SFN, stereochemistry specified per study

organism

Human, 45 women

plain_language

This preparation showed no thyroid signal under the conditions tested; that is not universal thyroid safety proof.

primary_references

[sulforaphane-p30735751] Broccoli sprout beverage is safe for thyroid hormonal and autoimmune status: Results of a 12-week randomized trial. (2019). https://pubmed.ncbi.nlm.nih.gov/30735751/ DOI: 10.1016/j.fct.2019.02.004

tissue_or_cell_type

Serum thyroid hormones, thyroglobulin and autoimmunity

Sulforaphane: formation, electrophile sensing and nutrient connections (2026-09-17) · lines 1217–1228

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Thyroid safety analysis within a randomized beverage trial · source_derived_draft · unverified_draft

### sulforaphane-thyroid-markers TSH, free thyroxine, thyroglobulin and thyroid autoimmunity status were not affected in this 84-day analysis. Condition category: normal nutrient_topic: Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. plain_language: This preparation showed no thyroid signal under the conditions tested; that is not universal thyroid safety proof. organism: Human, 45 women tissue_or_cell_type: Serum thyroid hormones, thyroglobulin and autoimmunity experimental_model: Thyroid safety analysis within a randomized beverage trial limitations: Subsample safety analysis; not all populations, iodine-deficient states, products, doses or lifelong exposure. exposure: Baseline and 84 days of glucoraphanin/sulforaphane-rich beverage evidence_span: {"source_cache": "artifacts/sulforaphane-research/30735751.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0797bbf31c4a1fa8cf002b8752410e80a92e8a351c44273335bc52f19e66b2ea", "start_char": 0, "end_char": 1494, "text_sha256": "0797bbf31c4a1fa8cf002b8752410e80a92e8a351c44273335bc52f19e66b2ea"} [sulforaphane-p30735751] Broccoli sprout beverage is safe for thyroid hormonal and autoimmune status: Results of a 12-week randomized trial. (2019). https://pubmed.ncbi.nlm.nih.gov/30735751/ DOI: 10.1016/j.fct.2019.02.004

evidence_access

Primary abstract

experimental_model

Five groups of ten; randomized, double-blind placebo-controlled treatment periods.

limitations

Specific iatrogenic hyperthyroidism context; does not justify changing thyroid medication or establish universal safety.

nutrient_topic

L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine

plain_language

A small clinical trial tested peripheral thyroid-hormone effects.

primary_references

Usefulness of L-carnitine, a naturally occurring peripheral antagonist of thyroid hormone action, in iatrogenic hyperthyroidism: a randomized, double-blind, placebo-controlled clinical trial. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11502782/ · DOI 10.1210/jcem.86.8.7747

L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 306–312

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Five groups of ten; randomized, double-blind placebo-controlled treatment periods. · source_derived_draft · unverified_draft

## l-carnitine-thyroid-clinical A small clinical trial tested peripheral thyroid-hormone effects. In a six-month trial of 50 women on fixed TSH-suppressive thyroxine, 2 or 4 g/day carnitine reduced or limited several hyperthyroid symptoms during treatment periods. Model: Five groups of ten; randomized, double-blind placebo-controlled treatment periods. Limitations: Specific iatrogenic hyperthyroidism context; does not justify changing thyroid medication or establish universal safety. Evidence access: Primary abstract Usefulness of L-carnitine, a naturally occurring peripheral antagonist of thyroid hormone action, in iatrogenic hyperthyroidism: a randomized, double-blind, placebo-controlled clinical trial. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11502782/ · DOI 10.1210/jcem.86.8.7747

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

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

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

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

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

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

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

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

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

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

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

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

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

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

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

true

evidence_location

Primary indexed abstract.

experimental_model

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

exposure

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

limitations

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

nutrient_topic

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

organism

Homo sapiens

plain_language

This iron–iodine trial also found a hormone response.

primary_references

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

tissue_or_cell_type

Thyroid volume, circulating thyroxine and iron indices

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

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

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

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

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

true

evidence_location

Primary indexed abstract.

experimental_model

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

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

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

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

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

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

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

evidence_span

{"source_cache": "artifacts/cold-research/1636702.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4e0d8127d3ebb682588afd84b635d2607dce9ebec4e7573d25e7baae58fc9301", "start_char": 0, "end_char": 1183, "text_sha256": "4e0d8127d3ebb682588afd84b635d2607dce9ebec4e7573d25e7baae58fc9301"}

experimental_model

Sixteen men given oral T3 before, during and after 80 cold air exposures, with and without T3 replacement

exposure

Eighty exposures to 4 degrees C air, ten per week

limitations

Cold air rather than water immersion, recorded because it isolates the thyroid hormone kinetics. The pharmacological oral T3 dose is not physiological.

nutrient_topic

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

organism

Human

plain_language

Cold makes the body consume active thyroid hormone faster, independently of the usual feedback loop.

primary_references

[cold-p1636702] Multiple cold air exposures change oral triiodothyronine kinetics in normal men. (1992). https://pubmed.ncbi.nlm.nih.gov/1636702/ DOI: 10.1152/ajpendo.1992.263.1.e85

tissue_or_cell_type

Whole body thyroid hormone kinetics

Cold water immersion: cold sensing, heat production, the catecholamine axis and what repeated exposure changes (2026-09-19) · lines 676–687

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Sixteen men given oral T3 before, during and after 80 cold air exposures, with and without T3 replacement · source_derived_draft · unverified_draft

### cold-cold-t3-clearance Repeated cold air exposure increased the oral metabolic clearance rate of T3 by 5.4 l/day/m2 and the disposal rate by 10.2 nmol/day/m2, and these increases were not dependent on thyrotropin or thyroxine, since they were unchanged in men given replacement T3 whose TSH and T4 fell by about half. Condition category: normal nutrient_topic: Cold water immersion research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Cold makes the body consume active thyroid hormone faster, independently of the usual feedback loop. organism: Human tissue_or_cell_type: Whole body thyroid hormone kinetics experimental_model: Sixteen men given oral T3 before, during and after 80 cold air exposures, with and without T3 replacement limitations: Cold air rather than water immersion, recorded because it isolates the thyroid hormone kinetics. The pharmacological oral T3 dose is not physiological. exposure: Eighty exposures to 4 degrees C air, ten per week evidence_span: {"source_cache": "artifacts/cold-research/1636702.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4e0d8127d3ebb682588afd84b635d2607dce9ebec4e7573d25e7baae58fc9301", "start_char": 0, "end_char": 1183, "text_sha256": "4e0d8127d3ebb682588afd84b635d2607dce9ebec4e7573d25e7baae58fc9301"} [cold-p1636702] Multiple cold air exposures change oral triiodothyronine kinetics in normal men. (1992). https://pubmed.ncbi.nlm.nih.gov/1636702/ DOI: 10.1152/ajpendo.1992.263.1.e85

evidence_span

{"source_cache": "artifacts/cold-research/11696583.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "adbd82ff8c43d8a2718cfa752c9a0607c367648d6573b968eb885c883376dc68", "start_char": 0, "end_char": 1332, "text_sha256": "adbd82ff8c43d8a2718cfa752c9a0607c367648d6573b968eb885c883376dc68"}

experimental_model

Mice with targeted disruption of the Dio2 gene, with brown adipocyte assays and T3 rescue

exposure

Cold stress, with norepinephrine, CL316,243 or forskolin stimulation, and a single T3 injection

limitations

The selenoenzyme is the link between thyroid hormone and sympathetic signalling. Plasma T3 was normal in the knockouts, so the defect is local hormone generation, not circulating hormone.

nutrient_topic

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

organism

Mouse

plain_language

Cold makes brown fat build a selenium enzyme that manufactures active thyroid hormone on the spot.

primary_references

[cold-p11696583] The type 2 iodothyronine deiodinase is essential for adaptive thermogenesis in brown adipose tissue. (2001). https://pubmed.ncbi.nlm.nih.gov/11696583/ DOI: 10.1172/jci13803

tissue_or_cell_type

Brown adipose tissue

Cold water immersion: cold sensing, heat production, the catecholamine axis and what repeated exposure changes (2026-09-19) · lines 377–388

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mice with targeted disruption of the Dio2 gene, with brown adipocyte assays and T3 rescue · source_derived_draft · unverified_draft

### cold-dio2-selenoenzyme Type 2 iodothyronine deiodinase is a selenoenzyme, the product of the cAMP-dependent Dio2 gene, which increases 10- to 50-fold during cold stress only in brown adipose tissue. Condition category: normal nutrient_topic: Cold water immersion research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Cold makes brown fat build a selenium enzyme that manufactures active thyroid hormone on the spot. organism: Mouse tissue_or_cell_type: Brown adipose tissue experimental_model: Mice with targeted disruption of the Dio2 gene, with brown adipocyte assays and T3 rescue limitations: The selenoenzyme is the link between thyroid hormone and sympathetic signalling. Plasma T3 was normal in the knockouts, so the defect is local hormone generation, not circulating hormone. exposure: Cold stress, with norepinephrine, CL316,243 or forskolin stimulation, and a single T3 injection evidence_span: {"source_cache": "artifacts/cold-research/11696583.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "adbd82ff8c43d8a2718cfa752c9a0607c367648d6573b968eb885c883376dc68", "start_char": 0, "end_char": 1332, "text_sha256": "adbd82ff8c43d8a2718cfa752c9a0607c367648d6573b968eb885c883376dc68"} [cold-p11696583] The type 2 iodothyronine deiodinase is essential for adaptive thermogenesis in brown adipose tissue. (2001). https://pubmed.ncbi.nlm.nih.gov/11696583/ DOI: 10.1172/jci13803

evidence_access

Primary abstract

experimental_model

Eight kinetic studies in seven thyrotoxic women; serum lithium about 1 mEq/L.

limitations

Compartment-model inference; not evidence that lithium simply removes iodine from the body.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

Making thyroid hormone and releasing it are separate steps.

primary_references

The use of lithium in the treatment of thyrotoxicosis. · 1972 · https://pubmed.ncbi.nlm.nih.gov/4115707/ · DOI 10.1172/JCI107094

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 392–398

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Eight kinetic studies in seven thyrotoxic women; serum lithium about 1 mEq/L. · source_derived_draft · unverified_draft

## lithium-thyroid-release Making thyroid hormone and releasing it are separate steps. Lithium reduced hormonal and nonhormonal thyroid iodine release in human radioiodine kinetic studies. Model: Eight kinetic studies in seven thyrotoxic women; serum lithium about 1 mEq/L. Limitations: Compartment-model inference; not evidence that lithium simply removes iodine from the body. Evidence access: Primary abstract The use of lithium in the treatment of thyrotoxicosis. · 1972 · https://pubmed.ncbi.nlm.nih.gov/4115707/ · DOI 10.1172/JCI107094

evidence_access

Primary abstract

experimental_model

Human radioiodine compartment modeling.

limitations

Not demonstrated inhibition of a particular deiodinase; do not infer selenium depletion.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

Blood hormone concentration reflects both release and removal.

primary_references

The use of lithium in the treatment of thyrotoxicosis. · 1972 · https://pubmed.ncbi.nlm.nih.gov/4115707/ · DOI 10.1172/JCI107094

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 400–406

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human radioiodine compartment modeling. · source_derived_draft · unverified_draft

## lithium-thyroid-turnover Blood hormone concentration reflects both release and removal. Five kinetic studies also required slower serum hormone disappearance to fit lithium-associated observations. Model: Human radioiodine compartment modeling. Limitations: Not demonstrated inhibition of a particular deiodinase; do not infer selenium depletion. Evidence access: Primary abstract The use of lithium in the treatment of thyrotoxicosis. · 1972 · https://pubmed.ncbi.nlm.nih.gov/4115707/ · DOI 10.1172/JCI107094

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

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/)

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)

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)