Vitamin D
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
- Vitamin D
- Vitamin D: From Nutritional Supplementation (No Indication Text on File) to Primary Release Disorder of Platelets
Vitamin D: From Nutritional Supplementation (No Indication Text on File) to Primary Release Disorder of Platelets
One-Sentence Summary
Vitamin D is used for nutritional supplementation and calcium/bone health. In Singapore it is registered only as a component of a combination tablet, and no approved-indication text was available in the data compiled for this report. The TxGNN model's top-ranked prediction is primary release disorder of platelets, but this rests on a graph-based score alone, with 0 clinical trials and 3 publications of unclear relevance. Other predictions have more support, notably hypoparathyroidism (5 retrieved trials, none directly testing vitamin D versus control) and sclerosing cholangitis (observational data only).
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not available (approved indication text is blank on the Singapore license) |
| Predicted New Indication | Primary release disorder of platelets |
| TxGNN Prediction Score | 93.11% |
| Evidence Level | L5 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 1 |
| Recommended Decision | Hold |
Other predictions in the top 10 (for context):
| Rank | Predicted Indication | TxGNN Score | Evidence Level | Recommendation |
|---|---|---|---|---|
| 1 | Primary release disorder of platelets | 93.11% | L5 | Hold |
| 2 | Sclerosing cholangitis | 92.38% | L3 | Research question |
| 3 | Pseudo-von Willebrand disease | 91.52% | L5 | Hold |
| 4 | Cholecystolithiasis | 90.57% | L4 | Hold |
| 5 | Multiple endocrine neoplasia | 90.19% | L4 | Hold |
| 6 | Glanzmann thrombasthenia | 87.80% | L5 | Hold |
| 7 | Familial isolated hypoparathyroidism (impaired PTH secretion) | 85.16% | L5 | Hold |
| 8 | Acromesomelic dysplasia, Campailla Martinelli type | 85.06% | L5 | Hold |
| 9 | Hypoparathyroidism | 84.07% | L3 | Proceed with Guardrails |
| 10 | Craniofacial conodysplasia | 83.91% | L5 | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available. Vitamin D is known to regulate calcium and phosphate homeostasis and to have immunomodulatory effects, but no established mechanistic link to platelet release (secretion) disorders was identified. The top-ranked prediction is therefore a graph-based association and not a mechanism-supported hypothesis.
The predictions with a more plausible rationale lie elsewhere in the list:
- Hypoparathyroidism (rank 9): Without parathyroid hormone, the kidney cannot efficiently activate vitamin D, and calcium control is impaired. Calcitriol or active vitamin D analogs plus calcium are long-established standard care. This is an existing clinical use and not a novel repurposing. The related genetic form (rank 7) is mechanistically plausible by extension, but has no trials or literature.
- Sclerosing cholangitis (rank 2): Vitamin D deficiency is common in primary sclerosing cholangitis because cholestasis impairs absorption of fat-soluble vitamins, and severe deficiency has prognostic significance. A 2026 cohort study associates supplementation with lower hepatobiliary malignancy risk. The evidence is observational, so this is better regarded as supportive care than disease-modifying treatment.
- Cholecystolithiasis (rank 4) and multiple endocrine neoplasia (rank 5): Cross-sectional data link low vitamin D to gallbladder stasis and gallstones, and vitamin D matters for calcium/PTH balance in MEN1-related hyperparathyroidism. Causality is unclear, and in MEN any role would be supportive management.
- Pseudo-von Willebrand disease, Glanzmann thrombasthenia, and the skeletal dysplasias (ranks 3, 6, 8, 10): No plausible vitamin D mechanism was identified.
Clinical Trial Evidence
The top-ranked prediction (primary release disorder of platelets) has no registered clinical trials. Trials were retrieved for two other predictions, and none directly tests vitamin D against a control in the predicted disease.
Hypoparathyroidism (rank 9)
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00001304 | Phase 2 | Completed | 27 | Synthetic PTH(1-34) in hypoparathyroidism, compared with conventional calcium and calcitriol therapy |
| NCT07491601 | Not applicable | Recruiting | 336 | Early PTH measurement to prevent symptomatic hypoparathyroidism after thyroid surgery |
| NCT07381998 | Not applicable | Enrolling by invitation | 150 | Parathyroid function and quality of life after total thyroidectomy |
| NCT00581828 | Phase 4 | Completed | 19 | Whether treating hypovitaminosis D improves calcium absorption (not hypoparathyroidism patients) |
| NCT01971411 | Not applicable | Completed | 60 | Vitamin D deficiency in elderly African American women (not related to hypoparathyroidism) |
Multiple endocrine neoplasia (rank 5)
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT01437696 | Phase 4 | Completed | 77 | Vitamin D dosing against winter deficiency in veterans (no MEN patients) |
| NCT03408119 | Not applicable | Completed | 62 | Dried plums and bone health in osteopenic men (not vitamin D; not related to MEN) |
Literature Evidence
Primary release disorder of platelets (rank 1)
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 27885969 | 2016 | Conference abstract | Critical Care | Intensive care symposium abstracts; no direct relevance to platelet release disorders |
| 31637855 | 2019 | Veterinary cohort | J Vet Emerg Crit Care | 25-OH vitamin D levels in critically ill dogs; not a platelet disorder |
| 42016165 | 2026 | Mendelian randomization | Int J Chron Obstruct Pulmon Dis | Blood metabolites, including vitamin D, and COPD risk in East Asians; not relevant to platelets |
Sclerosing cholangitis (rank 2), most relevant items
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 42467982 | 2026 | Cohort | Hepatology Communications | Vitamin D supplementation associated with reduced hepatobiliary malignancy risk in PSC |
| 36771282 | 2023 | Cohort | Nutrients | Severe vitamin D deficiency has prognostic significance in PSC (n = 354) |
| 25191532 | 2014 | Preclinical | Hepatology International | Vitamin D modulates biliary fibrosis in a mouse model of sclerosing cholangitis |
| 23845396 | 2013 | Review | Clin Res Hepatol Gastroenterol | Immunomodulatory role of vitamin D in autoimmune liver disease |
Hypoparathyroidism (rank 9), most relevant items
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 39905273 | 2025 | Review | Nat Rev Endocrinol | Diagnosis, management and emerging therapies for hypoparathyroidism |
| 37000405 | 2023 | Review | Endocrine | Vitamin D pathophysiology and clinical practice in hypoparathyroidism; active vitamin D (calcitriol) is conventional treatment |
| 36382754 | 2022 | Review | Arch Endocrinol Metab | Conventional therapy with vitamin D analogs and calcium salts versus PTH analogs |
| 30551988 | 2018 | Review | Best Pract Res Clin Endocrinol Metab | Oral calcium and/or active vitamin D are the cornerstones of chronic treatment |
Other predictions
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 27696253 | 2016 | Cross-sectional | Endocrine | Circulating 25-OH vitamin D and gallstones in a Danish population sample (cholecystolithiasis) |
| 26507741 | 2015 | Commentary | Dig Dis Sci | Vitamin D deficiency and gallbladder stasis (cholecystolithiasis) |
| 32276412 | 2020 | Review | Nutrients | Bone metabolism and vitamin D in neuroendocrine tumours (MEN) |
| 38892509 | 2024 | Review | Nutrients | Role of nutrition in managing MEN1 (MEN) |
| 42064390 | 2026 | Case report | Leuk Res Rep | Coexisting Glanzmann thrombasthenia and juvenile polyposis; no vitamin D-specific relevance |
No literature was retrieved for pseudo-von Willebrand disease, familial isolated hypoparathyroidism, acromesomelic dysplasia, or craniofacial conodysplasia.
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN13152P | Fosamax Plus™ 70mg/2800IU Tablet | Tablet (oral) | Not available |
This is a single-ingredient-registered license on file, valid, and the only registration for this drug in Singapore.
Safety Considerations
- Drug Interactions: The interaction screen returned 79 potential interactions, but severity levels are unclassified. Listed partners include calcitriol, vitamin A, doxycycline, acetylsalicylic acid, dexamethasone, prednisone, budesonide, triamcinolone, metformin, omeprazole, pantoprazole, lansoprazole, glimepiride, and morphine. Clinical significance needs confirmation.
- Class-level caution (from the literature): Vitamin D supplements and active analogs can cause hypercalcemia and hypercalciuria (nephrocalcinosis risk), so serum and urinary calcium should be monitored, particularly in hypoparathyroidism.
Please refer to the package insert for warnings and contraindications.
Conclusion and Next Steps
Decision: Hold (for the top-ranked prediction, primary release disorder of platelets)
Rationale: The top prediction is supported only by a graph-based score, with no trials and no relevant literature, and no plausible mechanism. Among the other predictions, hypoparathyroidism could proceed with guardrails, but it is an established use of vitamin D and active analogs and not a novel repurposing. Sclerosing cholangitis is a reasonable research question based on observational data.
To proceed, the following is needed:
- Package insert warnings and contraindications from the HSA (a blocking gap for safety screening)
- Mechanism of action data
- Approved indication text for the Singapore registration
- For hypoparathyroidism: confirmation of the product form (nutritional vitamin D versus active analogs) and a calcium monitoring plan
- For sclerosing cholangitis: prospective or interventional data on vitamin D as more than repletion for deficiency
- Severity classification of the 79 flagged drug interactions
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.