Safety Profile
Known Safety Concerns
- Prescription drug in most countries — self-supplementation is high-risk
- Hypercalcaemia at doses that would be harmless as D3
- Renal and cardiovascular toxicity at elevated calcium levels
- No safety buffer — requires regular calcium and PTH monitoring
Contraindications
- Prescription drug in most countries — self-supplementation is high-risk
- Hypercalcaemia at doses that would be harmless as D3
Interactions
Information not yet available for this ingredient profile.
Evidence and Scientific Findings
Ingredient Overview
Calcitriol is the active hormonal form of vitamin D, sold as a supplement for targeted applications. Unlike D3, calcitriol bypasses hepatic and renal activation and acts directly on vitamin D receptors. This makes it far more potent and dangerous — hypercalcaemia can occur at relatively small doses. It is a prescription drug in most countries. Self-supplementation with calcitriol without medical supervision carries significant risk.
Biological and Chemical Classification
- Scientific Name
- 1,25-Dihydroxycholecalciferol (Calcitriol)
Mechanism of Action
Information not yet available for this ingredient profile.
Clinical Evidence of Effectiveness
Information not yet available for this ingredient profile.
Pharmacokinetics
Information not yet available for this ingredient profile.
Recommended Dosage
Information not yet available for this ingredient profile.
SETI — Scientific Evidence Transparency Index
Executive Summary — Ingredient Assessment
- 10 studies reviewed
- 0 high-quality studies (meta-analysis or RCT)
- Main clinical benefit observed: Vitamin
- Evidence consistency: High consistency across studies (100%)
- Prescription drug in most countries — self-supplementation is high-risk
- Hypercalcaemia at doses that would be harmless as D3
- Renal and cardiovascular toxicity at elevated calcium levels
- No safety buffer — requires regular calcium and PTH monitoring
The available scientific evidence for Vitamin D (Calcitriol) indicates notable safety signals that warrant caution. Use should be considered carefully and monitored, particularly in sensitive populations or alongside other medications.
Total SETI Score
High risk| Evidence quality | 10/40 |
| Evidence consistency | 20/20 |
| Safety signals | 0/20 |
| Study recency | 10/10 |
| Evidence transparency | 10/10 |
Evidence Summary
- 10 studies reviewed
- 0 high-quality studies (meta-analysis or systematic review)
- 0 studies identified benefits or no safety concern (GREEN)
- 10 studies reported limited or advisory safety evidence (YELLOW)
Evidence Policy
Only peer-reviewed scientific literature indexed in PubMed or comparable databases is included in this evaluation. Commercial websites, blogs, and marketing materials are excluded. All references include direct traceable links to source documents.
Last updated: 23 მარ 2026, 15:06
Evidence Distribution
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Observational / other LOW evidence YELLOWLeveraging menstrual effluent (ME) to investigate vitamin D and human decidualization, a potential link with fertility. ↗Metz CN et al.. Leveraging menstrual effluent (ME) to investigate vitamin D and human decidualization, a potential link with fertility.. J Clin Endocrinol Metab. 2026. PMID:41492807.PMID 41492807 ↗Journal J Clin Endocrinol MetabYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41492807/
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Observational / other LOW evidence YELLOWCalcitriol's role in fetal bone and mineral metabolism: Evidence from human and animal studies. ↗Kovacs CS. Calcitriol's role in fetal bone and mineral metabolism: Evidence from human and animal studies.. J Steroid Biochem Mol Biol. 2026. PMID:41223950.PMID 41223950 ↗Journal J Steroid Biochem Mol BiolYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41223950/
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Observational / other LOW evidence YELLOWSearch for Potential VDR/Partner Composite Elements in Regulatory DNA of Genes Associated with Respiratory Infections and Atopic Diseases. ↗Popov AV et al.. Search for Potential VDR/Partner Composite Elements in Regulatory DNA of Genes Associated with Respiratory Infections and Atopic Diseases.. Int J Mol Sci. 2025. PMID:41516283.PMID 41516283 ↗Journal Int J Mol SciYear 2025Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41516283/
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Observational / other LOW evidence YELLOWThe Role of Vitamin D in Retinal Physiology. ↗Stoica AM et al.. The Role of Vitamin D in Retinal Physiology.. Rom J Ophthalmol. 2025. PMID:41189788.PMID 41189788 ↗Journal Rom J OphthalmolYear 2025Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41189788/
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Observational / other LOW evidence YELLOWA Rare Cause of Sacral Insufficiency Fracture in Adolescence: Autosomal Dominant Hypophosphatemic Rickets due to Fgf23 de novo P.Arg176trp Variant. ↗Aytau00e7 Kaplan EH et al.. A Rare Cause of Sacral Insufficiency Fracture in Adolescence: Autosomal Dominant Hypophosphatemic Rickets due to Fgf23 de novo P.Arg176trp Variant.. J Clin Res Pediatr Endocrinol. 2025. PMID:41165099.PMID 41165099 ↗Journal J Clin Res Pediatr EndocrinolYear 2025Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41165099/
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Observational / other LOW evidence YELLOWExpression of fibroblast growth factor 23 (FGF23) and u03b1Klotho in two commercial laying hen strains fed with and without dietary mineral P… ↗Meier L et al.. Expression of fibroblast growth factor 23 (FGF23) and u03b1Klotho in two commercial laying hen strains fed with and without dietary mineral P supplements before and after the onset of the laying phase.. Poult Sci. 2025. PMID:40834590.PMID 40834590 ↗Journal Poult SciYear 2025Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/40834590/
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Observational / other LOW evidence YELLOWPseudohypoparathyroidism with normocalcemia: a rare case report from Nepal. ↗Adhikari J et al.. Pseudohypoparathyroidism with normocalcemia: a rare case report from Nepal.. Ann Med Surg (Lond). 2025. PMID:40851936.PMID 40851936 ↗Journal Ann Med Surg (Lond)Year 2025Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/40851936/
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Observational / other LOW evidence YELLOWRegulation of u03b1Klotho. ↗Vogt J et al.. Regulation of u03b1Klotho.. Cell Physiol Biochem. 2025. PMID:40784026.PMID 40784026 ↗Journal Cell Physiol BiochemYear 2025Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/40784026/
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Observational / other LOW evidence YELLOWGenetic Polymorphism of CYP2R1, CYP27A1, CYP27B1, and Vitamin D Metabolites Plasma Levels in Patients with Cardiovascular Disease: A Pilot Study. ↗Abouzid M et al.. Genetic Polymorphism of CYP2R1, CYP27A1, CYP27B1, and Vitamin D Metabolites Plasma Levels in Patients with Cardiovascular Disease: A Pilot Study.. Biomolecules. 2025. PMID:40427592.PMID 40427592 ↗Journal BiomoleculesYear 2025Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/40427592/
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Observational / other LOW evidence YELLOWAntepartum high dietary supply of calcium affects bone homeostasis and offspring growth in dairy sheep and dairy goats. ↗Brugger D et al.. Antepartum high dietary supply of calcium affects bone homeostasis and offspring growth in dairy sheep and dairy goats.. J Dairy Sci. 2025. PMID:40139371.PMID 40139371 ↗Journal J Dairy SciYear 2025Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/40139371/
Score Transparency
0 of 10 approved references (score saturates at 10). More peer-reviewed studies = stronger evidence base.
Method: Q = number of approved references ÷ 10 (capped at 1.0)
Limited — mostly case reports or animal studies
Method: L = mean study-level weight across approved references. Level 1 (meta-analysis / systematic review) = 1.0; Level 2 (RCT) = 0.8; Level 3 (cohort/case-control) = 0.6; Level 4 (case report) = 0.4; Level 5 (animal / in-vitro) = 0.2.
Mixed or neutral — roughly equal benefit and risk signals
Method: D = (sum of risk-scored references − sum of benefit-scored references) ÷ total evidence score, then scaled from [−1, 1] to [0, 1]. 0.0 = pure benefit; 0.5 = neutral; 1.0 = pure risk.
One or more monitoring-level safety signals active
Method: S = 0.5 (neutral baseline) + sum of active signal severity deltas ÷ 10. Severity deltas: Critical = +2.0, High = +1.5, Moderate = +1.0, Low = +0.5. Capped at 1.0.
Final GIRI Score for Vitamin D (Calcitriol). Risk level thresholds: Low 0–3.0 · Moderate 3.0–5.5 · High 5.5–7.5 · Critical 7.5–10.
Full methodology & data sources
The GIRI Score is computed entirely from structured data — no editorial scoring or subjective weighting is applied at any step.
- References: Only approved references are counted. Each reference is assigned an evidence level (L1–L5) and a direction (risk / neutral / benefit) by the reference manager or AI classifier.
- Safety Signals: Sourced from regulatory agencies (FDA, EMA, Health Canada, TGA, and others) and pharmacovigilance databases. Only active signals count toward the score.
- Formula version: GIRI Score v3.7.0 — Q × L × D × S × 10.
- Limitations: The score reflects published evidence and recorded signals as of the last update date. It is not a clinical risk assessment and should not replace advice from a qualified healthcare professional.
Risk Level Classification
Based on available regulatory signals and scientific evidence, this ingredient presents a high safety concern. Its use in dietary supplements is associated with documented adverse events.
0–3.0
3.0–5.5
5.5–7.5
7.5–10
The score pin shows exactly where this ingredient falls on the fixed risk scale.
What drove the High classification for Vitamin D (Calcitriol)
A score of 6.5 places this ingredient in the High band. Thresholds: Low 0–3.0 · Moderate 3.0–5.5 · High 5.5–7.5 · Critical 7.5–10.
0 approved references.
Limited — mostly case reports or animal studies (Level 4–5).
Neutral or mixed — benefit and risk signals roughly balanced.
No active signals — S component is at neutral baseline (0.5), contributing no extra risk weight.
No major regulatory restrictions or advisories recorded across monitored jurisdictions (FDA, EMA, Health Canada, TGA, and others).
How are the Low / Moderate / High / Critical thresholds defined?
The four risk levels are fixed score bands. A score is assigned to exactly one level based on where it falls:
| Level | Score | Meaning |
|---|---|---|
| LOW | 0.0 – 2.9 | Sparse or predominantly beneficial evidence. No active safety alerts. |
| MODERATE | 3.0 – 5.4 | Mixed signals — some risk alongside benefit. Caution at high doses or in sensitive groups. |
| HIGH | 5.5 – 7.4 | Multiple studies or regulatory alerts documenting adverse effects. Professional oversight recommended. |
| CRITICAL | 7.5 – 10 | Regulatory restrictions in one or more major jurisdictions. Serious documented harm. Avoid without specialist supervision. |
Thresholds are fixed constants (GIRI_Score_Utils::LEVEL_THRESHOLDS). They do not change per ingredient and are never subject to editorial adjustment.