Global Ingredient Risk Index Vitamin

Vitamin D (Calcitriol)

1,25-Dihydroxycholecalciferol (Calcitriol)

Also known as: Calcitriol, 1,25-dihydroxyvitamin D, active vitamin D, Rocaltrol

23 მარ 2026

HIGH RISK 6.5/10 How?

This ingredient is classified as unclassified risk (GIRI score: 6.5/10).

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

═══════════════════════════════════════════════════════════════════════ -->

Information not yet available for this ingredient profile.

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.

Scientific Name: 1,25-Dihydroxycholecalciferol (Calcitriol)

Information not yet available for this ingredient profile.

SETI Score 50/100

Risk Level High risk

Scientific Confidence Low

Evidence Strength Limited

Key Benefit Vitamin

Key Safety Concern Prescription drug in most countries — self-supplementation is high-risk

Evidence Reviewed 10 PubMed studies

Scientific Confidence Low

Based on study quality, consistency, and recency

Executive Summary — Ingredient Assessment

SETI Score 50/100

Risk Level High risk

Evidence Strength Limited

Main Benefit Vitamin

Main Safety Concern Prescription drug in most countries — self-supplementation is high-risk

Ingredient Vitamin D (Calcitriol)

Scientific name 1,25-Dihydroxycholecalciferol (Calcitriol)

Scientific Evidence Overview

10 studies reviewed
0 high-quality studies (meta-analysis or RCT)
Main clinical benefit observed: Vitamin
Evidence consistency: High consistency across studies (100%)

Safety Signals

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

Evidence Strength Limited

Final Scientific Assessment

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.

Ingredient Vitamin D (Calcitriol)

Evidence reviewed 10 peer-reviewed studies (last 10 years)

Scientific name 1,25-Dihydroxycholecalciferol (Calcitriol)

50 /100

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

10 Other / unclassified

Observational / other LOW evidence YELLOW
Leveraging menstrual effluent (ME) to investigate vitamin D and human decidualization, a potential link with fertility. ↗

PMID 41492807 ↗

Journal J Clin Endocrinol Metab

Year 2026

Study type Observational / other

Evidence strength LOW evidence

PubMed link https://pubmed.ncbi.nlm.nih.gov/41492807/

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.
Observational / other LOW evidence YELLOW
Calcitriol's role in fetal bone and mineral metabolism: Evidence from human and animal studies. ↗

PMID 41223950 ↗

Journal J Steroid Biochem Mol Biol

Year 2026

Study type Observational / other

Evidence strength LOW evidence

PubMed link https://pubmed.ncbi.nlm.nih.gov/41223950/

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.
Observational / other LOW evidence YELLOW
Search for Potential VDR/Partner Composite Elements in Regulatory DNA of Genes Associated with Respiratory Infections and Atopic Diseases. ↗

PMID 41516283 ↗

Journal Int J Mol Sci

Year 2025

Study type Observational / other

Evidence strength LOW evidence

PubMed link https://pubmed.ncbi.nlm.nih.gov/41516283/

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.
Observational / other LOW evidence YELLOW
The Role of Vitamin D in Retinal Physiology. ↗

PMID 41189788 ↗

Journal Rom J Ophthalmol

Year 2025

Study type Observational / other

Evidence strength LOW evidence

PubMed link https://pubmed.ncbi.nlm.nih.gov/41189788/

Stoica AM et al.. The Role of Vitamin D in Retinal Physiology.. Rom J Ophthalmol. 2025. PMID:41189788.
Observational / other LOW evidence YELLOW
A Rare Cause of Sacral Insufficiency Fracture in Adolescence: Autosomal Dominant Hypophosphatemic Rickets due to Fgf23 de novo P.Arg176trp Variant. ↗

PMID 41165099 ↗

Journal J Clin Res Pediatr Endocrinol

Year 2025

Study type Observational / other

Evidence strength LOW evidence

PubMed link https://pubmed.ncbi.nlm.nih.gov/41165099/

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.
Observational / other LOW evidence YELLOW
Expression of fibroblast growth factor 23 (FGF23) and u03b1Klotho in two commercial laying hen strains fed with and without dietary mineral P… ↗

PMID 40834590 ↗

Journal Poult Sci

Year 2025

Study type Observational / other

Evidence strength LOW evidence

PubMed link https://pubmed.ncbi.nlm.nih.gov/40834590/

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.
Observational / other LOW evidence YELLOW
Pseudohypoparathyroidism with normocalcemia: a rare case report from Nepal. ↗

PMID 40851936 ↗

Journal Ann Med Surg (Lond)

Year 2025

Study type Observational / other

Evidence strength LOW evidence

PubMed link https://pubmed.ncbi.nlm.nih.gov/40851936/

Adhikari J et al.. Pseudohypoparathyroidism with normocalcemia: a rare case report from Nepal.. Ann Med Surg (Lond). 2025. PMID:40851936.
Observational / other LOW evidence YELLOW
Regulation of u03b1Klotho. ↗

PMID 40784026 ↗

Journal Cell Physiol Biochem

Year 2025

Study type Observational / other

Evidence strength LOW evidence

PubMed link https://pubmed.ncbi.nlm.nih.gov/40784026/

Vogt J et al.. Regulation of u03b1Klotho.. Cell Physiol Biochem. 2025. PMID:40784026.
Observational / other LOW evidence YELLOW
Genetic Polymorphism of CYP2R1, CYP27A1, CYP27B1, and Vitamin D Metabolites Plasma Levels in Patients with Cardiovascular Disease: A Pilot Study. ↗

PMID 40427592 ↗

Journal Biomolecules

Year 2025

Study type Observational / other

Evidence strength LOW evidence

PubMed link https://pubmed.ncbi.nlm.nih.gov/40427592/

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.
Observational / other LOW evidence YELLOW
Antepartum high dietary supply of calcium affects bone homeostasis and offspring growth in dairy sheep and dairy goats. ↗

PMID 40139371 ↗

Journal J Dairy Sci

Year 2025

Study type Observational / other

Evidence strength LOW evidence

PubMed link https://pubmed.ncbi.nlm.nih.gov/40139371/

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.

Q × L × D × S × 10 = 6.5 / 10

The GIRI Score is the product of four independently computed evidence components, each normalised to 0–1, then scaled to 0–10. Every component is derived exclusively from peer-reviewed references and regulatory data — no editorial judgement is applied.

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)

50%

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.

Benefit

Risk

50%

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.

50%

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.

0Q × 5L × 5D × 5S = 6.5 / 10

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.

HIGH RISK 6.5/10

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.

LOW
0–3.0

MODERATE
3.0–5.5

HIGH
5.5–7.5

CRITICAL
7.5–10

6.5

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.

← Back to Ingredient Database

Vitamin D (Calcitriol)

Safety Profile

Known Safety Concerns

Contraindications

Interactions

Evidence and Scientific Findings

Ingredient Overview

Biological and Chemical Classification

Mechanism of Action

Clinical Evidence of Effectiveness

Pharmacokinetics

Recommended Dosage

SETI — Scientific Evidence Transparency Index

Executive Summary — Ingredient Assessment

Evidence Summary

Evidence Policy

Evidence Distribution

Score Transparency

Risk Level Classification

What drove the High classification for Vitamin D (Calcitriol)

ბოლო სიახლეები

500მლ პლასტმასის წყლის ბოთლები: ფარული საზოგადოებრივი ჯანმრთელობის რისკები

სკოლამდელი განათლება – მნიშვნელობა და გამოწვევები

ბავშვის უფლებები სკოლაში

პოპულარული ამბები

საუკეთესო ფილმები კულინარიის მოყვარულებისთვის

როგორ იყენებენ ახალგაზრდები ხელოვნურ ინტელექტს – სტუდენტების ხმა

კატეგორიები

ჩვენ შესახებ

გამოგვყევი სოციალურ ქსელებში