What is Vitamin D3?
Vitamin D3 (Cholecalciferol) is a fat-soluble secosteroid and essential hormone synthesized via skin UV-B exposure or dietary sources. In research contexts, high-dose D3 is provided in injection form (20000 IU/ml).
D3 is the active biological precursor to 1,25-dihydroxyvitamin D3 (Calcitriol), the hormonally active metabolite that controls calcium regulation, bone metabolism and immune function.
This information is for research and educational purposes only. No medical advice.
Comparison
Vitamin D3 and related entries
Entries from the TPD lexicon around bones and vitamins. Tap a card to open its entry.
Simplified: vitamin D provides calcium absorption, the two bone drugs act on bone building itself. 27
How it works
Vitamin D3 is hydroxylated in the liver to 25-hydroxyvitamin D [25(OH)D], the primary storage and circulating form. In the kidney, it is then hydroxylated to the active hormone 1,25-dihydroxyvitamin D3 (Calcitriol), which:
- Regulates intestinal absorption of calcium and phosphate
- Modulates bone remodeling through parathyroid hormone signaling
- Signals immune cell function via vitamin D receptor (VDR)
- Supports muscle protein synthesis and myocyte function
Where it acts
Where vitamin D acts
Tap a point or a card. Colour = vitamin D receptor, grey = finding from trials.
- Gut
The active form increases calcium absorption from the gut2
VDR - Bone
Deficiency leads to bone loss and fractures, a very high yearly amount to more fractures5
Observed in trials - Muscles
Small effect on strength, larger with deficiency and from 651
Observed in trials - Airways
12 percent lower odds of an acute respiratory infection3
Observed in trials - Heart and vessels
VITAL: no reduction in major cardiovascular events4
Observed in trials
Targets in the ChEMBL database7
Compound CHEMBL1042: one recorded mechanism, Agonist (ChEMBL), acts via the active form calcitriol.
- Gene
- VDR
- UniProt
- P11473
- ChEMBL
- CHEMBL1977
- Action
- Agonist (ChEMBL), acts via the active form calcitriol
Application and dosing
Dosing
Dosing, titration and syringe
Loading the dosing information …
- Getting started and stepping up, drawn as a staircase
- Units on the U-100 syringe for every step
- How long one vial lasts
What the research shows
Extensive literature supports vitamin D's role in:
- Bone metabolism and osteoporosis prevention
- Muscle strength and cardiac function
- Immune cell function and infection resistance
- Calcium homeostasis and parathyroid hormone regulation
Studies show vitamin D deficiency is associated with bone loss, muscle strength decline, increased infection risk and cardiovascular problems. Injected D3 is used in research to examine optimal serum concentrations.
Study results
What the trials measured
Interactive: switch tabs, tap points, show or hide arms. Arms are named relative to each other, no dosing advice.
Odds of an acute respiratory infection3
Change versus placebo in percent, analysis of 25 trials with individual data
Calculated as an odds ratio, so as odds rather than risk. With large single amounts the protection was not statistically significant.
Cases over a median of 5.3 years4
Number, 25,871 people aged 50 or 55 and over, vitamin D3 daily versus placebo
Neither difference was statistically significant. Too much calcium in the blood or other side effects did not occur more often.
Falls and fractures after a very high yearly amount5
Rate per 100 person-years, 2,256 women aged 70 and over, 3 to 5 years
The rise in falls was strongest in the first 3 months after dosing. The trial gave vitamin D3 by mouth, once in autumn or winter.
Research status
Where the research stands
A selection of registered trials with vitamin D3. The large trials gave it by mouth, several smaller ones as an injection into the muscle. As of 26 Oct 2026. 6
- Preclinical Biochemistry: calcium absorption via the active form
- Phase 1 no registered trial
- Phase 2 no registered trial
- Phase 3 3 trials, 2 completed
- Approval as a medicine (cholecalciferol)
Show all 8 trials on a timelineHide timeline
VITAL · NCT01169259 · 25,871 participants, started Jul 2010, primary endpoint planned Nov 2018. Tests several agents.
Registry entry ↗ · Results: Manson et al., New England Journal of Medicine, 2019
DO-HEALTH · NCT01745263 · 2,157 participants, started Dec 2012, primary endpoint reached Nov 2017. Tests several agents.
Registry entry ↗ · Results not yet in PubMed
NCT02443246 · 84 participants, started Nov 2014, primary endpoint reached Aug 2015.
Registry entry ↗ · Results not yet in PubMed
NCT00956839 · 40 participants, started Jul 2009, primary endpoint reached Jun 2010.
Registry entry ↗ · Results not yet in PubMed
ViDImmun · NCT01845142 · 40 participants, started Feb 2013, primary endpoint reached May 2013.
Registry entry ↗ · Results not yet in PubMed
NCT03233295 · 108 participants, started Oct 2014, primary endpoint reached Aug 2016.
Registry entry ↗ · Results not yet in PubMed
SUCCINCT · NCT01130311 · 259 participants, started Oct 2009, primary endpoint reached Apr 2010.
Registry entry ↗ · Results not yet in PubMed
EVIREST-D · NCT01430793 · 99 participants, started Nov 2011, primary endpoint reached Mar 2013.
Registry entry ↗ · Results not yet in PubMed
Bar: start to primary endpoint (planned for running trials). Green = completed, blue = progress until 26 Oct 2026.
Side effects
- Vitamin D toxicity: Acute toxicity is rare at moderate doses; chronic high-dose can lead to hypercalcemia (rare)
- Local irritation: Pain or swelling at injection site (mild, rare)
- Hypersensitivity: Very rare
- Systemic: Nausea, appetite loss, headache (only with toxicity, not therapeutic doses)
- Monitoring: Serum calcium and vitamin D levels should be monitored in long-term research protocols
Storage
Store cool and dry, protected from light (ideally 2-8°C). Keep vial in original carton. Use within 8 weeks of opening. Do not freeze. Visually inspect for cloudiness or particles before use.