Vitamin D3

evidence score

vitamin mineral

472 studies

CholecalciferolVitamin D25-hydroxyvitamin D+2 more

Vitamin D3 (cholecalciferol) is a fat-soluble secosteroid hormone precursor, synthesized in skin upon UV-B exposure and obtained through diet and supplementation. Converted to 25(OH)D3 (calcidiol) in liver, then to active 1,25(OH)2D3 (calcitriol) in kidneys. Calcitriol regulates calcium/phosphate homeostasis and activates vitamin D receptors (VDR) present in virtually every cell type. Deficiency (25-OH-D <20 ng/mL) is pandemic, affecting >40% of Americans. Beyond bone metabolism, VDR signaling regulates immunity, muscle function, cardiovascular health, and gene expression of hundreds of genes. Large RCTs (VITAL, etc.) have refined the CV/cancer benefit picture: mortality and cancer benefits seen in true deficiency; supplementation in already-replete individuals shows less clear benefit. Safe at standard doses; toxicity only at extreme doses (>10,000 IU/day long-term without monitoring).

Evidence

Moderate evidence

Safety

Unknown safety profile

Clinical Status

Approved

Research Sync

Feb 19, 2026

Dosing

Typical

5000 IU

1000 IURange10000 IU

FrequencyOnce daily oral with fat-containing meal

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Pharmacology

Half-life25(OH)D3: ~2–3 weeks

OnsetSerum 25-OH-D rises within days; clinical effects over weeks to months

DurationTissue stores persist weeks after cessation

Routes

oral

Evidence Score

Level B — Moderate

472 studies indexed · 19 meta-analyses

Scoring Factors

Volume(40%)~53/100

Quality(30%)~52/100

Sample Size(10%)~100/100

Consistency(10%)~100/100

Replication(5%)~100/100

Recency(5%)~100/100

Scores estimated from study counts. Exact breakdown computed after research sync.

Evidence Levels

AScore ≥75 with at least 1 meta-analysis and 3+ RCTs

BScore ≥50 with at least 1 RCT or meta-analysis

CScore ≥25 — observational or animal evidence only

DScore <25 — very limited or preclinical data

Plain-English Snapshot

Vitamin D3 is currently categorized as a vitamin mineral compound.

Evidence is moderate (75/100): promising signal from 472 indexed studies, but context and population still matter.

Safety scoring is incomplete. Start conservatively and monitor carefully.

Core mechanism

Precursor to calcitriol; binds vitamin D receptor (nuclear receptor) in all cell types; regulates calcium homeostasis, immunity, muscle function, and expression of 200+ genes

Practical Context

Strongest current signals

Level A: The role of vitamin D and the VDR gene polymorphism in sepsis risk and mortality: a systematic review and meta-analysis.
Level B: The Effects of Marine Fatty Acid Omega-3 Supplements on Incident Fractures and Bone Mineral Density in Generally Healthy Adults.
Level B: Impact of vitamin D supplementation in the prognosis of patients with SARS-CoV2 pneumonia admitted to the intensive care unit - a randomized controlled trial.