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

Last Sync

Feb 19, 2026

Last Reviewed

Not reviewed yet

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(24%)~53/100

Quality(24%)~52/100

Sample Size(12%)~95/100

Consistency(14%)~95/100

Replication(8%)~95/100

Recency(18%)~95/100

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.