Parathyroid hormone / PTH

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

magnesium -> PTH -> calcium

experimental_model

Human hypomagnesemic hypocalcemia clinical study

limitations

Only two challenge studies; urinary cAMP is an organ-response marker, not direct measurement of PTH1R binding or adenylyl-cyclase Mg occupancy.

nutrient_topic

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

organism

Homo sapiens

plain_language

The kidney responded weakly to the PTH challenge, but another hormone/cAMP response remained functional; Mg deficiency did not disable all signaling equally.

primary_references

[rude-1976-human-pth-resistance] Functional hypoparathyroidism and parathyroid hormone end-organ resistance in human magnesium deficiency (1976). https://pubmed.ncbi.nlm.nih.gov/182417/ DOI: 10.1111/j.1365-2265.1976.tb01947.x

tissue_or_cell_type

Blood; parathyroid-kidney axis

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 337–347

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human hypomagnesemic hypocalcemia clinical study · source_derived_draft · unverified_draft

### mg-deficiency-blunts-renal-pth-camp-response Parathyroid extract produced only a small urinary cAMP response in the two Mg-deficient patients tested, while glucagon-stimulated plasma cAMP responses were preserved. Condition category: nutrient_deficiency nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The kidney responded weakly to the PTH challenge, but another hormone/cAMP response remained functional; Mg deficiency did not disable all signaling equally. organism: Homo sapiens tissue_or_cell_type: Blood; parathyroid-kidney axis experimental_model: Human hypomagnesemic hypocalcemia clinical study limitations: Only two challenge studies; urinary cAMP is an organ-response marker, not direct measurement of PTH1R binding or adenylyl-cyclase Mg occupancy. cross_nutrient: magnesium -> PTH -> calcium [rude-1976-human-pth-resistance] Functional hypoparathyroidism and parathyroid hormone end-organ resistance in human magnesium deficiency (1976). https://pubmed.ncbi.nlm.nih.gov/182417/ DOI: 10.1111/j.1365-2265.1976.tb01947.x

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

magnesium -> PTH -> calcium/phosphate

experimental_model

Single-child Mg withdrawal/repletion with hormone challenge

limitations

Single case; shows PTH resistance is not obligatory. Primary hypomagnesemia was not genetically assigned in this study.

nutrient_topic

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

organism

Homo sapiens

plain_language

In this child the main failure was releasing the hormone; tissues could still respond when hormone was provided.

primary_references

[suh-1973-preserved-pth-response] Pathogenesis of Hypocalcemia in Primary Hypomagnesemia: Normal End-Organ Responsiveness to Parathyroid Hormone, Impaired Parathyroid Gland Function (1973). https://www.jci.org/articles/view/107159 DOI: 10.1172/JCI107159

tissue_or_cell_type

Blood and kidney

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 397–407

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Single-child Mg withdrawal/repletion with hormone challenge · source_derived_draft · unverified_draft

### primary-hypomagnesemia-can-preserve-pth-response A child with primary hypomagnesemia retained calcemic and renal phosphate/cAMP responses to parathyroid extract during Mg depletion despite impaired endogenous PTH secretion. Condition category: nutrient_deficiency nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: In this child the main failure was releasing the hormone; tissues could still respond when hormone was provided. organism: Homo sapiens tissue_or_cell_type: Blood and kidney experimental_model: Single-child Mg withdrawal/repletion with hormone challenge limitations: Single case; shows PTH resistance is not obligatory. Primary hypomagnesemia was not genetically assigned in this study. cross_nutrient: magnesium -> PTH -> calcium/phosphate [suh-1973-preserved-pth-response] Pathogenesis of Hypocalcemia in Primary Hypomagnesemia: Normal End-Organ Responsiveness to Parathyroid Hormone, Impaired Parathyroid Gland Function (1973). https://www.jci.org/articles/view/107159 DOI: 10.1172/JCI107159

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

magnesium -> PTH response -> vitamin D/calcium

experimental_model

26 initially normal adults before/after three-week low-Mg diet

limitations

Circulating metabolite response does not identify CYP27B1 as a directly Mg-dependent enzyme or distinguish all production/clearance effects.

nutrient_topic

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

organism

Homo sapiens

plain_language

Even when PTH was supplied directly, the downstream vitamin-D response was reduced, supporting a target-organ component beyond reduced hormone release.

primary_references

[fatemi-1991-selective-depletion] Effect of experimental human magnesium depletion on parathyroid hormone secretion and 1,25-dihydroxyvitamin D metabolism. (1991). https://pubmed.ncbi.nlm.nih.gov/1939521/ DOI: 10.1210/jcem-73-5-1067

tissue_or_cell_type

Blood; parathyroid and renal mineral axis

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 385–395

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 26 initially normal adults before/after three-week low-Mg diet · source_derived_draft · unverified_draft

### selective-mg-depletion-blunts-pth-calcitriol-response The rise in circulating calcitriol during a six-hour human PTH(1-34) infusion was smaller after dietary Mg depletion. Condition category: nutrient_deficiency nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Even when PTH was supplied directly, the downstream vitamin-D response was reduced, supporting a target-organ component beyond reduced hormone release. organism: Homo sapiens tissue_or_cell_type: Blood; parathyroid and renal mineral axis experimental_model: 26 initially normal adults before/after three-week low-Mg diet limitations: Circulating metabolite response does not identify CYP27B1 as a directly Mg-dependent enzyme or distinguish all production/clearance effects. cross_nutrient: magnesium -> PTH response -> vitamin D/calcium [fatemi-1991-selective-depletion] Effect of experimental human magnesium depletion on parathyroid hormone secretion and 1,25-dihydroxyvitamin D metabolism. (1991). https://pubmed.ncbi.nlm.nih.gov/1939521/ DOI: 10.1210/jcem-73-5-1067

experimental_model

Daily PTH(1-34) administration and cell assays

limitations

An experimental dosing context; it must not be generalized to sustained endogenous PTH elevation or calcium supplementation.

nutrient_topic

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

organism

Mus musculus; rodent and human cell corroboration

plain_language

Intermittent PTH exposure can prolong the survival of bone-forming cells.

primary_references

[jilka1999] Increased bone formation by prevention of osteoblast apoptosis with parathyroid hormone (1999). https://www.jci.org/articles/view/6610 DOI: 10.1172/JCI6610

tissue_or_cell_type

Cancellous bone osteoblasts

Calcium: mechanism-first literature curation (2026-09-17) · lines 1093–1102

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Daily PTH(1-34) administration and cell assays · source_derived_draft · unverified_draft

### intermittent-pth-reduces-osteoblast-apoptosis Daily PTH(1-34) injections reduced osteoblast apoptosis and increased bone formation in the studied adult mouse strains. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Intermittent PTH exposure can prolong the survival of bone-forming cells. organism: Mus musculus; rodent and human cell corroboration tissue_or_cell_type: Cancellous bone osteoblasts experimental_model: Daily PTH(1-34) administration and cell assays limitations: An experimental dosing context; it must not be generalized to sustained endogenous PTH elevation or calcium supplementation. [jilka1999] Increased bone formation by prevention of osteoblast apoptosis with parathyroid hormone (1999). https://www.jci.org/articles/view/6610 DOI: 10.1172/JCI6610

availability_state

machinery_impairment Imported condition classification; unverified.

experimental_model

Low-calcium-fed rats; thyroparathyroidectomy and parathyroid-extract replacement

limitations

Surgical removal plus extract replacement; not a purified-enzyme assay.

nutrient_topic

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

organism

Rattus norvegicus

plain_language

Hormonal support helps activate vitamin D during calcium restriction.

primary_references

[garabedian1972] Control of 25-hydroxycholecalciferol metabolism by parathyroid glands (1972). https://pubmed.ncbi.nlm.nih.gov/4340153/ DOI: 10.1073/pnas.69.7.1673

tissue_or_cell_type

Systemic vitamin D metabolism

trigger_kind

machinery_impairment Imported condition classification; unverified.

Calcium: mechanism-first literature curation (2026-09-17) · lines 69–78

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Low-calcium-fed rats; thyroparathyroidectomy and parathyroid-extract replacement · source_derived_draft · unverified_draft

### parathyroid-loss-calcitriol-production Thyroparathyroidectomy nearly abolished calcitriol production in low-calcium-fed rats; parathyroid extract restored it. Condition category: machinery_impairment nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Hormonal support helps activate vitamin D during calcium restriction. organism: Rattus norvegicus tissue_or_cell_type: Systemic vitamin D metabolism experimental_model: Low-calcium-fed rats; thyroparathyroidectomy and parathyroid-extract replacement limitations: Surgical removal plus extract replacement; not a purified-enzyme assay. [garabedian1972] Control of 25-hydroxycholecalciferol metabolism by parathyroid glands (1972). https://pubmed.ncbi.nlm.nih.gov/4340153/ DOI: 10.1073/pnas.69.7.1673

experimental_model

HEK293 expression, calcium uptake, FRET, patch clamp and TRPV5 mutagenesis

limitations

Response required strong intracellular calcium buffering; cultured-cell mechanism.

nutrient_topic

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

organism

Heterologous HEK293 expression system

plain_language

PTH can increase calcium entry through TRPV5.

primary_references

[degroot2009] Parathyroid hormone activates TRPV5 via PKA-dependent phosphorylation (2009). https://pmc.ncbi.nlm.nih.gov/articles/PMC2723979/ DOI: 10.1681/ASN.2008080873

tissue_or_cell_type

Plasma membrane; distal-nephron mechanism

Calcium: mechanism-first literature curation (2026-09-17) · lines 58–67

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · HEK293 expression, calcium uptake, FRET, patch clamp and TRPV5 mutagenesis · source_derived_draft · unverified_draft

### pth-activates-trpv5 PTH increases TRPV5 activity through cAMP-PKA-dependent phosphorylation at T709 in receptor/channel expression assays. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: PTH can increase calcium entry through TRPV5. organism: Heterologous HEK293 expression system tissue_or_cell_type: Plasma membrane; distal-nephron mechanism experimental_model: HEK293 expression, calcium uptake, FRET, patch clamp and TRPV5 mutagenesis limitations: Response required strong intracellular calcium buffering; cultured-cell mechanism. [degroot2009] Parathyroid hormone activates TRPV5 via PKA-dependent phosphorylation (2009). https://pmc.ncbi.nlm.nih.gov/articles/PMC2723979/ DOI: 10.1681/ASN.2008080873

availability_state

biomarker_context Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/biotin-research/28973622.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4ee7e5947d8391b7a0fa7601d8390147b99c5ff603b3462e9d1aa7f3db42b915", "start_char": 20261, "end_char": 20798, "text_sha256": "440bd38aad94623f97cd7f956c63815b7a25d790328c4407bcdf6d24f8d2be0d"}

experimental_model

Nonrandomized crossover study of 6 healthy adults, 37 assays and 11 analytes

exposure

10 mg oral biotin daily for 7 days

limitations

Interference depends on assay architecture and version; this study does not establish current platform performance, a universal washout time or true hormone changes.

nutrient_topic

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

organism

Homo sapiens

plain_language

A falsely low PTH result can misleadingly suggest a problem in calcium regulation.

primary_references

[b7-p28973622] Association of Biotin Ingestion With Performance of Hormone and Nonhormone Assays in Healthy Adults. (2017). https://pubmed.ncbi.nlm.nih.gov/28973622/ DOI: 10.1001/jama.2017.13705

tissue_or_cell_type

Blood specimens measured on named 2017 assay systems

trigger_kind

biomarker_context Imported condition classification; unverified.

Biotin: carboxylases, recycling, deficiency and nutrient interactions (2026-09-17) · lines 1261–1272

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Nonrandomized crossover study of 6 healthy adults, 37 assays and 11 analytes · source_derived_draft · unverified_draft

### b7-assay-pth The studied Vitros 5600 PTH assay fell by a mean 61% after biotin, while serum calcium remained stable. Condition category: biomarker_context nutrient_topic: Biotin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A falsely low PTH result can misleadingly suggest a problem in calcium regulation. organism: Homo sapiens tissue_or_cell_type: Blood specimens measured on named 2017 assay systems experimental_model: Nonrandomized crossover study of 6 healthy adults, 37 assays and 11 analytes limitations: Interference depends on assay architecture and version; this study does not establish current platform performance, a universal washout time or true hormone changes. exposure: 10 mg oral biotin daily for 7 days evidence_span: {"source_cache": "artifacts/biotin-research/28973622.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4ee7e5947d8391b7a0fa7601d8390147b99c5ff603b3462e9d1aa7f3db42b915", "start_char": 20261, "end_char": 20798, "text_sha256": "440bd38aad94623f97cd7f956c63815b7a25d790328c4407bcdf6d24f8d2be0d"} [b7-p28973622] Association of Biotin Ingestion With Performance of Hormone and Nonhormone Assays in Healthy Adults. (2017). https://pubmed.ncbi.nlm.nih.gov/28973622/ DOI: 10.1001/jama.2017.13705

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

magnesium -> PTH -> calcium

experimental_model

Human hypomagnesemic hypocalcemia clinical study

limitations

Delay is indirect evidence for resistance and does not by itself identify a receptor or cyclase defect.

nutrient_topic

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

organism

Homo sapiens

plain_language

Restoring the hormone signal did not immediately restore calcium; this pattern suggested an additional target-organ response problem.

primary_references

[rude-1976-human-pth-resistance] Functional hypoparathyroidism and parathyroid hormone end-organ resistance in human magnesium deficiency (1976). https://pubmed.ncbi.nlm.nih.gov/182417/ DOI: 10.1111/j.1365-2265.1976.tb01947.x

tissue_or_cell_type

Blood; parathyroid-kidney axis

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 325–335

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human hypomagnesemic hypocalcemia clinical study · source_derived_draft · unverified_draft

### calcium-recovery-can-lag-pth-after-mg During early Mg repletion, PTH recovered before serum calcium normalized in the serially studied patients. Condition category: nutrient_deficiency nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Restoring the hormone signal did not immediately restore calcium; this pattern suggested an additional target-organ response problem. organism: Homo sapiens tissue_or_cell_type: Blood; parathyroid-kidney axis experimental_model: Human hypomagnesemic hypocalcemia clinical study limitations: Delay is indirect evidence for resistance and does not by itself identify a receptor or cyclase defect. cross_nutrient: magnesium -> PTH -> calcium [rude-1976-human-pth-resistance] Functional hypoparathyroidism and parathyroid hormone end-organ resistance in human magnesium deficiency (1976). https://pubmed.ncbi.nlm.nih.gov/182417/ DOI: 10.1111/j.1365-2265.1976.tb01947.x

cross_nutrient

magnesium -> PTH -> calcium

experimental_model

Graded extracellular cations in cultured bovine parathyroid slices

limitations

Potency depends on concentrations and preparation; no general human replacement ratio follows.

nutrient_topic

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

organism

Bos taurus

plain_language

Both ions can signal the gland to release less PTH; calcium and magnesium are not interchangeable inputs.

primary_references

[habener-1976-pth-synthesis-secretion] Relative effectiveness of magnesium and calcium on the secretion and biosynthesis of parathyroid hormone in vitro (1976). https://pubmed.ncbi.nlm.nih.gov/1248443/ DOI: 10.1210/endo-98-1-197

tissue_or_cell_type

Parathyroid gland

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 253–263

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Graded extracellular cations in cultured bovine parathyroid slices · source_derived_draft · unverified_draft

### mg-ca-differential-pth-secretory-potency In bovine parathyroid slices, extracellular Mg and Ca inhibited PTH release additively, but Mg was less potent on a molar basis. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Both ions can signal the gland to release less PTH; calcium and magnesium are not interchangeable inputs. organism: Bos taurus tissue_or_cell_type: Parathyroid gland experimental_model: Graded extracellular cations in cultured bovine parathyroid slices limitations: Potency depends on concentrations and preparation; no general human replacement ratio follows. cross_nutrient: magnesium -> PTH -> calcium [habener-1976-pth-synthesis-secretion] Relative effectiveness of magnesium and calcium on the secretion and biosynthesis of parathyroid hormone in vitro (1976). https://pubmed.ncbi.nlm.nih.gov/1248443/ DOI: 10.1210/endo-98-1-197

cross_nutrient

magnesium -> PTH -> calcium

experimental_model

Radiolabeled leucine incorporation and precursor/hormone analysis

limitations

A negative result in this exposure range does not exclude synthesis defects during prolonged severe deficiency.

nutrient_topic

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

organism

Bos taurus

plain_language

Mg changed release of the hormone without showing the same effect on making or processing it in this assay.

primary_references

[habener-1976-pth-synthesis-secretion] Relative effectiveness of magnesium and calcium on the secretion and biosynthesis of parathyroid hormone in vitro (1976). https://pubmed.ncbi.nlm.nih.gov/1248443/ DOI: 10.1210/endo-98-1-197

tissue_or_cell_type

Parathyroid gland

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 265–275

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Radiolabeled leucine incorporation and precursor/hormone analysis · source_derived_draft · unverified_draft

### mg-does-not-change-pth-biosynthesis-in-slice-assay Mg concentration did not measurably change PTH biosynthesis or proPTH-to-PTH conversion in the bovine slice experiments. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Mg changed release of the hormone without showing the same effect on making or processing it in this assay. organism: Bos taurus tissue_or_cell_type: Parathyroid gland experimental_model: Radiolabeled leucine incorporation and precursor/hormone analysis limitations: A negative result in this exposure range does not exclude synthesis defects during prolonged severe deficiency. cross_nutrient: magnesium -> PTH -> calcium [habener-1976-pth-synthesis-secretion] Relative effectiveness of magnesium and calcium on the secretion and biosynthesis of parathyroid hormone in vitro (1976). https://pubmed.ncbi.nlm.nih.gov/1248443/ DOI: 10.1210/endo-98-1-197

cross_nutrient

magnesium -> PTH -> calcium

experimental_model

Intact rat parathyroid glands in graded Ca/Mg media

limitations

An ex-vivo concentration response, not a human threshold; very high 5 mM Mg produced broader suppression.

nutrient_topic

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

organism

Rattus norvegicus

plain_language

How much extra Mg reduces PTH depends on the calcium signal already reaching the gland.

primary_references

[rodriguez-ortiz-2014-pth-context] Magnesium modulates parathyroid hormone secretion and upregulates parathyroid receptor expression at moderately low calcium concentration (2014). https://pubmed.ncbi.nlm.nih.gov/24103811/ DOI: 10.1093/ndt/gft400

tissue_or_cell_type

Parathyroid gland

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 277–287

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Intact rat parathyroid glands in graded Ca/Mg media · source_derived_draft · unverified_draft

### mg-pth-inhibition-depends-on-calcium In intact rat glands, raising Mg from 0.5 to 2 mM suppressed PTH most clearly at moderately low Ca; suppression was small or absent at normal-high Ca and diminished again at very low Ca. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: How much extra Mg reduces PTH depends on the calcium signal already reaching the gland. organism: Rattus norvegicus tissue_or_cell_type: Parathyroid gland experimental_model: Intact rat parathyroid glands in graded Ca/Mg media limitations: An ex-vivo concentration response, not a human threshold; very high 5 mM Mg produced broader suppression. cross_nutrient: magnesium -> PTH -> calcium [rodriguez-ortiz-2014-pth-context] Magnesium modulates parathyroid hormone secretion and upregulates parathyroid receptor expression at moderately low calcium concentration (2014). https://pubmed.ncbi.nlm.nih.gov/24103811/ DOI: 10.1093/ndt/gft400

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

magnesium -> PTH -> calcium

experimental_model

Acute Mg administration across clinical groups

limitations

Biphasic/status-dependent response does not establish one serum Mg breakpoint applicable to all patients.

nutrient_topic

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

organism

Homo sapiens

plain_language

Restoring missing Mg can release a suppressed PTH response, while adding Mg in another starting state can inhibit it.

primary_references

[rude-1978-status-dependent-pth] Parathyroid hormone secretion in magnesium deficiency (1978). https://pubmed.ncbi.nlm.nih.gov/263326/ DOI: 10.1210/jcem-47-4-800

tissue_or_cell_type

Blood; parathyroid axis

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 349–359

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Acute Mg administration across clinical groups · source_derived_draft · unverified_draft

### mg-pth-response-depends-on-prior-status Mg administration promptly raised PTH in hypomagnesemic patients, whereas normal and hyperparathyroid comparison groups showed a decrease or little change. Condition category: nutrient_deficiency nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Restoring missing Mg can release a suppressed PTH response, while adding Mg in another starting state can inhibit it. organism: Homo sapiens tissue_or_cell_type: Blood; parathyroid axis experimental_model: Acute Mg administration across clinical groups limitations: Biphasic/status-dependent response does not establish one serum Mg breakpoint applicable to all patients. cross_nutrient: magnesium -> PTH -> calcium [rude-1978-status-dependent-pth] Parathyroid hormone secretion in magnesium deficiency (1978). https://pubmed.ncbi.nlm.nih.gov/263326/ DOI: 10.1210/jcem-47-4-800

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

magnesium -> PTH -> calcium

experimental_model

26 initially normal adults before/after three-week low-Mg diet

limitations

Before/after experiment; not a population diagnostic rule. Depletion was supported by serum Mg, retention, and red-cell free Mg changes.

nutrient_topic

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

organism

Homo sapiens

plain_language

PTH compensation was impaired during an induced shortage, before a failed calcium-replacement attempt was needed to reveal it.

primary_references

[fatemi-1991-selective-depletion] Effect of experimental human magnesium depletion on parathyroid hormone secretion and 1,25-dihydroxyvitamin D metabolism. (1991). https://pubmed.ncbi.nlm.nih.gov/1939521/ DOI: 10.1210/jcem-73-5-1067

tissue_or_cell_type

Blood; parathyroid and renal mineral axis

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 361–371

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 26 initially normal adults before/after three-week low-Mg diet · source_derived_draft · unverified_draft

### selective-mg-depletion-impairs-pth-compensation After selective dietary Mg depletion, 20 of 26 adults showed unchanged or reduced PTH despite falling serum Mg and Ca. Condition category: nutrient_deficiency nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: PTH compensation was impaired during an induced shortage, before a failed calcium-replacement attempt was needed to reveal it. organism: Homo sapiens tissue_or_cell_type: Blood; parathyroid and renal mineral axis experimental_model: 26 initially normal adults before/after three-week low-Mg diet limitations: Before/after experiment; not a population diagnostic rule. Depletion was supported by serum Mg, retention, and red-cell free Mg changes. cross_nutrient: magnesium -> PTH -> calcium [fatemi-1991-selective-depletion] Effect of experimental human magnesium depletion on parathyroid hormone secretion and 1,25-dihydroxyvitamin D metabolism. (1991). https://pubmed.ncbi.nlm.nih.gov/1939521/ DOI: 10.1210/jcem-73-5-1067

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

magnesium -> calcium

experimental_model

26 initially normal adults before/after three-week low-Mg diet

limitations

Mean change in a small controlled study; not evidence that every mildly low Mg value causes clinical hypocalcemia.

nutrient_topic

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

organism

Homo sapiens

plain_language

Calcium regulation changed during experimental Mg shortage even without a preceding calcium-repletion failure.

primary_references

[fatemi-1991-selective-depletion] Effect of experimental human magnesium depletion on parathyroid hormone secretion and 1,25-dihydroxyvitamin D metabolism. (1991). https://pubmed.ncbi.nlm.nih.gov/1939521/ DOI: 10.1210/jcem-73-5-1067

tissue_or_cell_type

Blood; parathyroid and renal mineral axis

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 373–383

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 26 initially normal adults before/after three-week low-Mg diet · source_derived_draft · unverified_draft

### selective-mg-depletion-lowers-circulating-calcium Three weeks of selective Mg depletion produced a small but significant reduction in serum calcium in the adult study. Condition category: nutrient_deficiency nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Calcium regulation changed during experimental Mg shortage even without a preceding calcium-repletion failure. organism: Homo sapiens tissue_or_cell_type: Blood; parathyroid and renal mineral axis experimental_model: 26 initially normal adults before/after three-week low-Mg diet limitations: Mean change in a small controlled study; not evidence that every mildly low Mg value causes clinical hypocalcemia. cross_nutrient: magnesium -> calcium [fatemi-1991-selective-depletion] Effect of experimental human magnesium depletion on parathyroid hormone secretion and 1,25-dihydroxyvitamin D metabolism. (1991). https://pubmed.ncbi.nlm.nih.gov/1939521/ DOI: 10.1210/jcem-73-5-1067

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

magnesium -> PTH -> calcium

experimental_model

Human hypomagnesemic hypocalcemia clinical study

limitations

Observational baseline result; older immunoreactive PTH assays differ from modern intact-PTH methods.

nutrient_topic

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

organism

Homo sapiens

plain_language

A PTH value within a laboratory reference range can still be too low for someone whose calcium is very low.

primary_references

[rude-1976-human-pth-resistance] Functional hypoparathyroidism and parathyroid hormone end-organ resistance in human magnesium deficiency (1976). https://pubmed.ncbi.nlm.nih.gov/182417/ DOI: 10.1111/j.1365-2265.1976.tb01947.x

tissue_or_cell_type

Blood; parathyroid-kidney axis

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 301–311

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human hypomagnesemic hypocalcemia clinical study · source_derived_draft · unverified_draft

### severe-mg-deficiency-inadequate-pth-response Most untreated patients in the clinical series had normal or undetectable immunoreactive PTH despite severe hypocalcemia. Condition category: nutrient_deficiency nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A PTH value within a laboratory reference range can still be too low for someone whose calcium is very low. organism: Homo sapiens tissue_or_cell_type: Blood; parathyroid-kidney axis experimental_model: Human hypomagnesemic hypocalcemia clinical study limitations: Observational baseline result; older immunoreactive PTH assays differ from modern intact-PTH methods. cross_nutrient: magnesium -> PTH -> calcium [rude-1976-human-pth-resistance] Functional hypoparathyroidism and parathyroid hormone end-organ resistance in human magnesium deficiency (1976). https://pubmed.ncbi.nlm.nih.gov/182417/ DOI: 10.1111/j.1365-2265.1976.tb01947.x

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Vitamin D–calcium–phosphate regulation.

evidence_locator

Results: biochemical parameters, growth-plate histology and TUNEL; primary text excerpts cached in web-assay-excerpts.json

evidence_scope

D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison.

experimental_model

Wild-type mice fed high-calcium/low-phosphate diet; growth-plate histology and TUNEL assay

exposure

High-calcium/low-phosphate diet; biochemical comparisons at 24 days of age in Figure 2. Exact diet duration/formulation not resolved in retrieved passages.

limitations

The diet arm is separated from Vdr-null and Phex-mutant models. No single human serum threshold or claim that every rachitic disorder has one mechanism is inferred.

nutrient

Vitamin D2 and D3 · Vitamin D2 and D3

nutrient_topic

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

organism

Mus musculus

plain_language

Low phosphate disrupted maturation of growth-plate cartilage even when calcium was high.

primary_references

[vdm-sabbagh2005] Hypophosphatemia leads to rickets by impairing caspase-mediated apoptosis of hypertrophic chondrocytes. (2005). https://pubmed.ncbi.nlm.nih.gov/15976027/ DOI: 10.1073/pnas.0502249102

tissue_or_cell_type

Growth-plate hypertrophic chondrocytes

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 777–791

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Wild-type mice fed high-calcium/low-phosphate diet; growth-plate histology and TUNEL assay · source_derived_draft · unverified_draft

### vdm-phosphate-restriction-reduces-growth-plate-apoptosis Diet-induced hypophosphatemic mice had impaired late hypertrophic-chondrocyte apoptosis and rachitic growth-plate expansion despite hypercalcemia and suppressed PTH. Condition category: nutrient_deficiency nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Low phosphate disrupted maturation of growth-plate cartilage even when calcium was high. organism: Mus musculus tissue_or_cell_type: Growth-plate hypertrophic chondrocytes experimental_model: Wild-type mice fed high-calcium/low-phosphate diet; growth-plate histology and TUNEL assay limitations: The diet arm is separated from Vdr-null and Phex-mutant models. No single human serum threshold or claim that every rachitic disorder has one mechanism is inferred. exposure: High-calcium/low-phosphate diet; biochemical comparisons at 24 days of age in Figure 2. Exact diet duration/formulation not resolved in retrieved passages. cross_nutrient: Vitamin D–calcium–phosphate regulation. evidence_locator: Results: biochemical parameters, growth-plate histology and TUNEL; primary text excerpts cached in web-assay-excerpts.json nutrient: Vitamin D2 and D3 evidence_scope: D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison. [vdm-sabbagh2005] Hypophosphatemia leads to rickets by impairing caspase-mediated apoptosis of hypertrophic chondrocytes. (2005). https://pubmed.ncbi.nlm.nih.gov/15976027/ DOI: 10.1073/pnas.0502249102

experimental_model

Vitamin D metabolite administration to rats; parathyroid RNA and nuclear transcription assays

limitations

Administered hormone and transcription assay; does not resolve every promoter mechanism.

nutrient_topic

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

organism

Rattus norvegicus

plain_language

Active vitamin D feeds back on hormone production.

primary_references

[silver1986] Regulation by vitamin D metabolites of parathyroid hormone gene transcription in vivo in the rat (1986). https://pubmed.ncbi.nlm.nih.gov/3771798/ DOI: 10.1172/JCI112714

tissue_or_cell_type

Parathyroid

Calcium: mechanism-first literature curation (2026-09-17) · lines 80–89

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Vitamin D metabolite administration to rats; parathyroid RNA and nuclear transcription assays · source_derived_draft · unverified_draft

### calcitriol-suppresses-pth-transcription Calcitriol administration suppresses parathyroid PTH transcription in rats without a measured rise in serum calcium. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Active vitamin D feeds back on hormone production. organism: Rattus norvegicus tissue_or_cell_type: Parathyroid experimental_model: Vitamin D metabolite administration to rats; parathyroid RNA and nuclear transcription assays limitations: Administered hormone and transcription assay; does not resolve every promoter mechanism. [silver1986] Regulation by vitamin D metabolites of parathyroid hormone gene transcription in vivo in the rat (1986). https://pubmed.ncbi.nlm.nih.gov/3771798/ DOI: 10.1172/JCI112714

experimental_model

Bovine parathyroid cells and human CaSR-expressing HEK293 cells

limitations

Pharmacological cell experiment; potentiation required extracellular calcium.

nutrient_topic

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

organism

Bos taurus

plain_language

Greater calcium-sensor activation reduces hormone release.

primary_references

[nemeth1998] Calcimimetics with potent and selective activity on the parathyroid calcium receptor (1998). https://pmc.ncbi.nlm.nih.gov/articles/PMC19959/ DOI: 10.1073/pnas.95.7.4040

tissue_or_cell_type

Parathyroid cells

Calcium: mechanism-first literature curation (2026-09-17) · lines 25–34

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Bovine parathyroid cells and human CaSR-expressing HEK293 cells · source_derived_draft · unverified_draft

### casr-calcium-pth-suppression CaSR potentiation by NPS R-568 strengthens extracellular-calcium-mediated inhibition of PTH secretion in bovine parathyroid cells. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Greater calcium-sensor activation reduces hormone release. organism: Bos taurus tissue_or_cell_type: Parathyroid cells experimental_model: Bovine parathyroid cells and human CaSR-expressing HEK293 cells limitations: Pharmacological cell experiment; potentiation required extracellular calcium. [nemeth1998] Calcimimetics with potent and selective activity on the parathyroid calcium receptor (1998). https://pmc.ncbi.nlm.nih.gov/articles/PMC19959/ DOI: 10.1073/pnas.95.7.4040

availability_state

nutrient_deficiency Imported condition classification; unverified.

experimental_model

30 days of 0.01% versus 0.516% dietary calcium

limitations

Mouse diet and Cre-targeting scope limit human generalization; bone loss was blunted, not necessarily abolished.

nutrient_topic

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

organism

Mus musculus

plain_language

When dietary calcium was severely restricted, osteocyte RANKL helped drive withdrawal from bone.

primary_references

[xiong2014] Osteocyte-derived RANKL is a critical mediator of the increased bone resorption caused by dietary calcium deficiency (2014). https://pmc.ncbi.nlm.nih.gov/articles/PMC4125539/ DOI: 10.1016/j.bone.2014.06.006

tissue_or_cell_type

Adult cortical and cancellous bone

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Calcium: mechanism-first literature curation (2026-09-17) · lines 1070–1079

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 30 days of 0.01% versus 0.516% dietary calcium · source_derived_draft · unverified_draft

### low-calcium-diet-osteocyte-rankl-resorption A calcium-deficient diet increased osteoclasts and bone loss in adult mice; osteocyte-directed Rankl deletion blunted the response. Condition category: nutrient_deficiency nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: When dietary calcium was severely restricted, osteocyte RANKL helped drive withdrawal from bone. organism: Mus musculus tissue_or_cell_type: Adult cortical and cancellous bone experimental_model: 30 days of 0.01% versus 0.516% dietary calcium limitations: Mouse diet and Cre-targeting scope limit human generalization; bone loss was blunted, not necessarily abolished. [xiong2014] Osteocyte-derived RANKL is a critical mediator of the increased bone resorption caused by dietary calcium deficiency (2014). https://pmc.ncbi.nlm.nih.gov/articles/PMC4125539/ DOI: 10.1016/j.bone.2014.06.006

availability_state

nutrient_deficiency Imported condition classification; unverified.

experimental_model

Nine healthy women; controlled 2000-to-300 mg/day calcium diet change and oral 47Ca retention

limitations

Small controlled study; low intake is not proof of symptomatic deficiency.

nutrient_topic

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

organism

Homo sapiens

plain_language

Low intake recruits a hormonal response.

primary_references

[dawsonhughes1988] Effect of lowering dietary calcium intake on fractional whole body calcium retention (1988). https://pubmed.ncbi.nlm.nih.gov/3132484/ DOI: 10.1210/jcem-67-1-62

tissue_or_cell_type

Blood

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Calcium: mechanism-first literature curation (2026-09-17) · lines 291–300

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Nine healthy women; controlled 2000-to-300 mg/day calcium diet change and oral 47Ca retention · source_derived_draft · unverified_draft

### low-calcium-intake-increases-pth Reducing calcium intake from 2000 to 300 mg/day increased intact PTH within one week in nine healthy women. Condition category: nutrient_deficiency nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Low intake recruits a hormonal response. organism: Homo sapiens tissue_or_cell_type: Blood experimental_model: Nine healthy women; controlled 2000-to-300 mg/day calcium diet change and oral 47Ca retention limitations: Small controlled study; low intake is not proof of symptomatic deficiency. [dawsonhughes1988] Effect of lowering dietary calcium intake on fractional whole body calcium retention (1988). https://pubmed.ncbi.nlm.nih.gov/3132484/ DOI: 10.1210/jcem-67-1-62

availability_state

machinery_impairment Imported condition classification; unverified.

experimental_model

Mice with targeted disruption of the VDR DNA-binding domain

limitations

Global receptor deletion; not isolated dietary calcium shortage.

nutrient_topic

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

organism

Mus musculus

plain_language

Vitamin D receptor failure disrupts calcium regulation.

primary_references

[li1997] Targeted ablation of the vitamin D receptor: an animal model of vitamin D-dependent rickets type II with alopecia (1997). https://pmc.ncbi.nlm.nih.gov/articles/PMC23277/ DOI: 10.1073/pnas.94.18.9831

tissue_or_cell_type

Systemic mineral metabolism

trigger_kind

machinery_impairment Imported condition classification; unverified.

Calcium: mechanism-first literature curation (2026-09-17) · lines 135–144

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 VDR DNA-binding domain · source_derived_draft · unverified_draft

### vdr-loss-hypocalcemia VDR-ablated mice develop hypocalcemia around postnatal day 21 with rising PTH. Condition category: machinery_impairment nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin D receptor failure disrupts calcium regulation. organism: Mus musculus tissue_or_cell_type: Systemic mineral metabolism experimental_model: Mice with targeted disruption of the VDR DNA-binding domain limitations: Global receptor deletion; not isolated dietary calcium shortage. [li1997] Targeted ablation of the vitamin D receptor: an animal model of vitamin D-dependent rickets type II with alopecia (1997). https://pmc.ncbi.nlm.nih.gov/articles/PMC23277/ DOI: 10.1073/pnas.94.18.9831

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/chloride-research/11099045.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4929ed9da0f3702bbd28bf679f79c2dfb13b4e81d23e44327b27bebdcf3a7cca", "start_char": 0, "end_char": 1218, "text_sha256": "4929ed9da0f3702bbd28bf679f79c2dfb13b4e81d23e44327b27bebdcf3a7cca"}

experimental_model

Clcn5 knockout and uptake measurements

exposure

Clcn5 disruption

limitations

The PTH/vitamin-D/hypercalciuria explanation includes proposed downstream steps; do not treat every link as demonstrated.

nutrient_topic

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

organism

Mouse

plain_language

Hormone retrieval changed too, offering a possible route to altered mineral regulation.

primary_references

[chloride-p11099045] ClC-5 Cl- -channel disruption impairs endocytosis in a mouse model for Dent's disease. (2000). https://pubmed.ncbi.nlm.nih.gov/11099045/ DOI: 10.1038/35042597

tissue_or_cell_type

Proximal renal tubule

trigger_kind

machinery_impairment Imported condition classification; unverified.

Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 705–716

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Clcn5 knockout and uptake measurements · source_derived_draft · unverified_draft

### chloride-clc5-pth Tubular endocytosis of PTH was reduced in the Clcn5-null model. Condition category: machinery_impairment nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: Hormone retrieval changed too, offering a possible route to altered mineral regulation. organism: Mouse tissue_or_cell_type: Proximal renal tubule experimental_model: Clcn5 knockout and uptake measurements limitations: The PTH/vitamin-D/hypercalciuria explanation includes proposed downstream steps; do not treat every link as demonstrated. exposure: Clcn5 disruption evidence_span: {"source_cache": "artifacts/chloride-research/11099045.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4929ed9da0f3702bbd28bf679f79c2dfb13b4e81d23e44327b27bebdcf3a7cca", "start_char": 0, "end_char": 1218, "text_sha256": "4929ed9da0f3702bbd28bf679f79c2dfb13b4e81d23e44327b27bebdcf3a7cca"} [chloride-p11099045] ClC-5 Cl- -channel disruption impairs endocytosis in a mouse model for Dent's disease. (2000). https://pubmed.ncbi.nlm.nih.gov/11099045/ DOI: 10.1038/35042597

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Potassium -> calcium/phosphate/PTH observations.

experimental_model

Concurrent mineral and hormone measurements.

limitations

Co-occurrence does not establish that PTH caused every excretion change.

nutrient_topic

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

organism

Homo sapiens

plain_language

Potassium depletion affected calcium-phosphate regulation alongside sodium handling.

primary_references

[k-krishna1991] Potassium depletion exacerbates essential hypertension (1991). https://pubmed.ncbi.nlm.nih.gov/2058867/ DOI: 10.7326/0003-4819-115-2-77

tissue_or_cell_type

Plasma and urine

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1534–1544

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Concurrent mineral and hormone measurements. · source_derived_draft · unverified_draft

### k-depletion-human-mineral-pth-response The depletion period also increased urinary calcium and phosphate and plasma immunoreactive PTH. Condition category: nutrient_deficiency nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Potassium depletion affected calcium-phosphate regulation alongside sodium handling. organism: Homo sapiens tissue_or_cell_type: Plasma and urine experimental_model: Concurrent mineral and hormone measurements. limitations: Co-occurrence does not establish that PTH caused every excretion change. cross_nutrient: Potassium -> calcium/phosphate/PTH observations. [k-krishna1991] Potassium depletion exacerbates essential hypertension (1991). https://pubmed.ncbi.nlm.nih.gov/2058867/ DOI: 10.7326/0003-4819-115-2-77

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Dietary potassium restriction altered renal calcium balance, circulating PTH and trabecular mineral density; each endpoint is recorded independently.

endpoint

Dietary potassium restriction increased urinary calcium excretion in the male-mouse experiments.

experimental-exposure

Male mice; two-week potassium-free discovery study and four/eight-week low-potassium study; urine/plasma minerals, renal proteomics, skeletal imaging, and constitutively active SPAK model.

experimental_model

Male mice; two-week potassium-free discovery study and four/eight-week low-potassium study; urine/plasma minerals, renal proteomics, skeletal imaging, and constitutively active SPAK model.

limitations

Male mouse model; co-occurring renal transporter and endocrine changes do not prove a complete causal chain or a human fracture effect. NCC-specific mediation is incompletely isolated.

nutrient_topic

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

organism

Mus musculus

plain_language

The kidneys lost more calcium when dietary potassium was restricted.

primary_references

[murali-2026-calcium] Dietary potassium restriction causes hypercalciuria, hypocalcemia, and bone loss in male mice (2026). https://insight.jci.org/articles/view/196339 DOI: 10.1172/jci.insight.196339

tissue_or_cell_type

kidney, blood and trabecular skeleton

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1288–1300

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Male mice; two-week potassium-free discovery study and four/eight-week low-potassium study; urine/plasma minerals, renal proteomics, skeletal imaging, and constitutively active SPAK model. · source_derived_draft · unverified_draft

### mouse-k-restriction-calciuria Dietary potassium restriction increased urinary calcium excretion in the male-mouse experiments. Condition category: nutrient_deficiency nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The kidneys lost more calcium when dietary potassium was restricted. organism: Mus musculus tissue_or_cell_type: kidney, blood and trabecular skeleton experimental_model: Male mice; two-week potassium-free discovery study and four/eight-week low-potassium study; urine/plasma minerals, renal proteomics, skeletal imaging, and constitutively active SPAK model. limitations: Male mouse model; co-occurring renal transporter and endocrine changes do not prove a complete causal chain or a human fracture effect. NCC-specific mediation is incompletely isolated. cross_nutrient: Dietary potassium restriction altered renal calcium balance, circulating PTH and trabecular mineral density; each endpoint is recorded independently. experimental-exposure: Male mice; two-week potassium-free discovery study and four/eight-week low-potassium study; urine/plasma minerals, renal proteomics, skeletal imaging, and constitutively active SPAK model. endpoint: Dietary potassium restriction increased urinary calcium excretion in the male-mouse experiments. [murali-2026-calcium] Dietary potassium restriction causes hypercalciuria, hypocalcemia, and bone loss in male mice (2026). https://insight.jci.org/articles/view/196339 DOI: 10.1172/jci.insight.196339

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Dietary potassium restriction altered renal calcium balance, circulating PTH and trabecular mineral density; each endpoint is recorded independently.

endpoint

Dietary potassium restriction reduced measured plasma total calcium in the male mice.

experimental-exposure

Male mice; two-week potassium-free discovery study and four/eight-week low-potassium study; urine/plasma minerals, renal proteomics, skeletal imaging, and constitutively active SPAK model.

experimental_model

Male mice; two-week potassium-free discovery study and four/eight-week low-potassium study; urine/plasma minerals, renal proteomics, skeletal imaging, and constitutively active SPAK model.

limitations

Male mouse model; co-occurring renal transporter and endocrine changes do not prove a complete causal chain or a human fracture effect. NCC-specific mediation is incompletely isolated.

nutrient_topic

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

organism

Mus musculus

plain_language

Blood total calcium fell alongside increased urinary calcium loss.

primary_references

[murali-2026-calcium] Dietary potassium restriction causes hypercalciuria, hypocalcemia, and bone loss in male mice (2026). https://insight.jci.org/articles/view/196339 DOI: 10.1172/jci.insight.196339

tissue_or_cell_type

kidney, blood and trabecular skeleton

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1302–1314

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Male mice; two-week potassium-free discovery study and four/eight-week low-potassium study; urine/plasma minerals, renal proteomics, skeletal imaging, and constitutively active SPAK model. · source_derived_draft · unverified_draft

### mouse-k-restriction-low-calcium Dietary potassium restriction reduced measured plasma total calcium in the male mice. Condition category: nutrient_deficiency nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Blood total calcium fell alongside increased urinary calcium loss. organism: Mus musculus tissue_or_cell_type: kidney, blood and trabecular skeleton experimental_model: Male mice; two-week potassium-free discovery study and four/eight-week low-potassium study; urine/plasma minerals, renal proteomics, skeletal imaging, and constitutively active SPAK model. limitations: Male mouse model; co-occurring renal transporter and endocrine changes do not prove a complete causal chain or a human fracture effect. NCC-specific mediation is incompletely isolated. cross_nutrient: Dietary potassium restriction altered renal calcium balance, circulating PTH and trabecular mineral density; each endpoint is recorded independently. experimental-exposure: Male mice; two-week potassium-free discovery study and four/eight-week low-potassium study; urine/plasma minerals, renal proteomics, skeletal imaging, and constitutively active SPAK model. endpoint: Dietary potassium restriction reduced measured plasma total calcium in the male mice. [murali-2026-calcium] Dietary potassium restriction causes hypercalciuria, hypocalcemia, and bone loss in male mice (2026). https://insight.jci.org/articles/view/196339 DOI: 10.1172/jci.insight.196339

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Dietary potassium restriction altered renal calcium balance, circulating PTH and trabecular mineral density; each endpoint is recorded independently.

endpoint

The potassium-restricted male mice showed increased plasma parathyroid hormone.

experimental-exposure

Male mice; two-week potassium-free discovery study and four/eight-week low-potassium study; urine/plasma minerals, renal proteomics, skeletal imaging, and constitutively active SPAK model.

experimental_model

Male mice; two-week potassium-free discovery study and four/eight-week low-potassium study; urine/plasma minerals, renal proteomics, skeletal imaging, and constitutively active SPAK model.

limitations

Male mouse model; co-occurring renal transporter and endocrine changes do not prove a complete causal chain or a human fracture effect. NCC-specific mediation is incompletely isolated.

nutrient_topic

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

organism

Mus musculus

plain_language

The calcium-regulating hormone response accompanied altered calcium balance.

primary_references

[murali-2026-calcium] Dietary potassium restriction causes hypercalciuria, hypocalcemia, and bone loss in male mice (2026). https://insight.jci.org/articles/view/196339 DOI: 10.1172/jci.insight.196339

tissue_or_cell_type

kidney, blood and trabecular skeleton

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1316–1328

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Male mice; two-week potassium-free discovery study and four/eight-week low-potassium study; urine/plasma minerals, renal proteomics, skeletal imaging, and constitutively active SPAK model. · source_derived_draft · unverified_draft

### mouse-k-restriction-pth The potassium-restricted male mice showed increased plasma parathyroid hormone. Condition category: nutrient_deficiency nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The calcium-regulating hormone response accompanied altered calcium balance. organism: Mus musculus tissue_or_cell_type: kidney, blood and trabecular skeleton experimental_model: Male mice; two-week potassium-free discovery study and four/eight-week low-potassium study; urine/plasma minerals, renal proteomics, skeletal imaging, and constitutively active SPAK model. limitations: Male mouse model; co-occurring renal transporter and endocrine changes do not prove a complete causal chain or a human fracture effect. NCC-specific mediation is incompletely isolated. cross_nutrient: Dietary potassium restriction altered renal calcium balance, circulating PTH and trabecular mineral density; each endpoint is recorded independently. experimental-exposure: Male mice; two-week potassium-free discovery study and four/eight-week low-potassium study; urine/plasma minerals, renal proteomics, skeletal imaging, and constitutively active SPAK model. endpoint: The potassium-restricted male mice showed increased plasma parathyroid hormone. [murali-2026-calcium] Dietary potassium restriction causes hypercalciuria, hypocalcemia, and bone loss in male mice (2026). https://insight.jci.org/articles/view/196339 DOI: 10.1172/jci.insight.196339

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Dietary potassium restriction altered renal calcium balance, circulating PTH and trabecular mineral density; each endpoint is recorded independently.

endpoint

Prolonged low-potassium feeding reduced trabecular bone mineral density in the male-mouse study.

experimental-exposure

Male mice; two-week potassium-free discovery study and four/eight-week low-potassium study; urine/plasma minerals, renal proteomics, skeletal imaging, and constitutively active SPAK model.

experimental_model

Male mice; two-week potassium-free discovery study and four/eight-week low-potassium study; urine/plasma minerals, renal proteomics, skeletal imaging, and constitutively active SPAK model.

limitations

Male mouse model; co-occurring renal transporter and endocrine changes do not prove a complete causal chain or a human fracture effect. NCC-specific mediation is incompletely isolated.

nutrient_topic

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

organism

Mus musculus

plain_language

The mineral imbalance extended to a measured skeletal endpoint.

primary_references

[murali-2026-calcium] Dietary potassium restriction causes hypercalciuria, hypocalcemia, and bone loss in male mice (2026). https://insight.jci.org/articles/view/196339 DOI: 10.1172/jci.insight.196339

tissue_or_cell_type

kidney, blood and trabecular skeleton

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1330–1342

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Male mice; two-week potassium-free discovery study and four/eight-week low-potassium study; urine/plasma minerals, renal proteomics, skeletal imaging, and constitutively active SPAK model. · source_derived_draft · unverified_draft

### mouse-k-restriction-trabecular-bone Prolonged low-potassium feeding reduced trabecular bone mineral density in the male-mouse study. Condition category: nutrient_deficiency nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The mineral imbalance extended to a measured skeletal endpoint. organism: Mus musculus tissue_or_cell_type: kidney, blood and trabecular skeleton experimental_model: Male mice; two-week potassium-free discovery study and four/eight-week low-potassium study; urine/plasma minerals, renal proteomics, skeletal imaging, and constitutively active SPAK model. limitations: Male mouse model; co-occurring renal transporter and endocrine changes do not prove a complete causal chain or a human fracture effect. NCC-specific mediation is incompletely isolated. cross_nutrient: Dietary potassium restriction altered renal calcium balance, circulating PTH and trabecular mineral density; each endpoint is recorded independently. experimental-exposure: Male mice; two-week potassium-free discovery study and four/eight-week low-potassium study; urine/plasma minerals, renal proteomics, skeletal imaging, and constitutively active SPAK model. endpoint: Prolonged low-potassium feeding reduced trabecular bone mineral density in the male-mouse study. [murali-2026-calcium] Dietary potassium restriction causes hypercalciuria, hypocalcemia, and bone loss in male mice (2026). https://insight.jci.org/articles/view/196339 DOI: 10.1172/jci.insight.196339

availability_state

biomarker_context Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Seven lithium-treated women versus seven controls; mean set-point 5.08 versus 4.88 mg/dL ionized calcium.

limitations

Supports altered feedback, not direct lithium binding to human CaSR.

nutrient_topic

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

plain_language

Calcium feedback to the parathyroid gland was reset.

primary_references

Alterations in parathyroid dynamics in lithium-treated subjects. · 1997 · https://pubmed.ncbi.nlm.nih.gov/9284708/ · DOI 10.1210/jcem.82.9.4218

trigger_kind

biomarker_context Imported condition classification; unverified.

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 384–390

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Seven lithium-treated women versus seven controls; mean set-point 5.08 versus 4.88 mg/dL ionized calcium. · source_derived_draft · unverified_draft

## lithium-pth-setpoint Calcium feedback to the parathyroid gland was reset. Chronic lithium-treated patients required a higher calcium level for comparable PTH suppression during calcium/citrate infusions. Model: Seven lithium-treated women versus seven controls; mean set-point 5.08 versus 4.88 mg/dL ionized calcium. Limitations: Supports altered feedback, not direct lithium binding to human CaSR. Evidence access: Primary abstract Alterations in parathyroid dynamics in lithium-treated subjects. · 1997 · https://pubmed.ncbi.nlm.nih.gov/9284708/ · DOI 10.1210/jcem.82.9.4218

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_span

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experimental_model

Double-blind randomized comparison with physiological substudy

exposure

One treatment course of ferric carboxymaltose versus ferumoxytol; five-week follow-up

limitations

Formulation-specific pharmacological effect, not dietary iron or all intravenous iron. Trial funded by ferumoxytol manufacturer; mineral associations support but do not individually prove every causal arrow.

nutrient_topic

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

organism

1997 adults with iron-deficiency anemia; 185 in substudy

plain_language

The phosphate disturbance connected to active vitamin D and calcium-regulating hormones.

primary_references

[iron-p30518682] Randomized trial of intravenous iron-induced hypophosphatemia. (2018). https://pubmed.ncbi.nlm.nih.gov/30518682/ DOI: 10.1172/jci.insight.124486

tissue_or_cell_type

Blood and renal phosphate handling

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 979–990

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind randomized comparison with physiological substudy · source_derived_draft · unverified_draft

### iron-fgf23-vitamin-d-calcium The FGF23 rise was associated with lower calcitriol and serum calcium and higher PTH concentrations. Condition category: nutrient_deficiency nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: The phosphate disturbance connected to active vitamin D and calcium-regulating hormones. organism: 1997 adults with iron-deficiency anemia; 185 in substudy tissue_or_cell_type: Blood and renal phosphate handling experimental_model: Double-blind randomized comparison with physiological substudy limitations: Formulation-specific pharmacological effect, not dietary iron or all intravenous iron. Trial funded by ferumoxytol manufacturer; mineral associations support but do not individually prove every causal arrow. exposure: One treatment course of ferric carboxymaltose versus ferumoxytol; five-week follow-up evidence_span: {"source_cache": "artifacts/iron-research/30518682.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "489945718bb05c0630fd563dc5a6da0874e80685717ab06ceedfefc38d172257", "start_char": 0, "end_char": 2371, "text_sha256": "489945718bb05c0630fd563dc5a6da0874e80685717ab06ceedfefc38d172257"} [iron-p30518682] Randomized trial of intravenous iron-induced hypophosphatemia. (2018). https://pubmed.ncbi.nlm.nih.gov/30518682/ DOI: 10.1172/jci.insight.124486

evidence_span

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experimental_model

CaSR expression/mutagenesis and isolated human/mouse parathyroid experiments

exposure

Extracellular phosphate in pathophysiologic CKD ranges; R62A substitution and mouse Casr deletion

limitations

Direct phosphate antagonism was tested separately from calcium regulation; concentrations and model are not dietary thresholds.

nutrient_topic

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

organism

Human

plain_language

Human parathyroid cells responded directly to the phosphate challenge.

primary_references

[phosphorus-p31619668] Phosphate acts directly on the calcium-sensing receptor to stimulate parathyroid hormone secretion. (2019). https://pubmed.ncbi.nlm.nih.gov/31619668/ DOI: 10.1038/s41467-019-12399-9

tissue_or_cell_type

CaSR reporter cells and freshly isolated parathyroid cells/glands

Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 451–462

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · CaSR expression/mutagenesis and isolated human/mouse parathyroid experiments · source_derived_draft · unverified_draft

### phosphorus-human-pth Pathophysiologic phosphate concentrations rapidly and reversibly increased PTH secretion from freshly isolated human parathyroid cells. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: Human parathyroid cells responded directly to the phosphate challenge. organism: Human tissue_or_cell_type: CaSR reporter cells and freshly isolated parathyroid cells/glands experimental_model: CaSR expression/mutagenesis and isolated human/mouse parathyroid experiments limitations: Direct phosphate antagonism was tested separately from calcium regulation; concentrations and model are not dietary thresholds. exposure: Extracellular phosphate in pathophysiologic CKD ranges; R62A substitution and mouse Casr deletion evidence_span: {"source_cache": "artifacts/phosphorus-research/31619668.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e4fe1ed7eb92175f99f446afa19fb184147ceed0413f3a6dffa85aa80927015d", "start_char": 0, "end_char": 1144, "text_sha256": "e4fe1ed7eb92175f99f446afa19fb184147ceed0413f3a6dffa85aa80927015d"} [phosphorus-p31619668] Phosphate acts directly on the calcium-sensing receptor to stimulate parathyroid hormone secretion. (2019). https://pubmed.ncbi.nlm.nih.gov/31619668/ DOI: 10.1038/s41467-019-12399-9