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Lexicon

Vitamin D3

High-dose vitamin D3 (Cholecalciferol) to support bone, muscle and immune function in research contexts.

2 min read 7 sources

Vitamin D3 vial with yellowish solution, blue cap and the black TPD label on a white podium, next to a blue 3D molecule model with rings in a bright lab
Compound approved · as a medicine (cholecalciferol)

Summary

At a glance

Sources checked on 26 Oct 2026

Respiratory infections
−12 %

lower odds of an infection, 25 trials with 10,933 participants3

Largest trial
25,871 participants

VITAL: no reduction in cancer or cardiovascular events over 5.3 years4

More falls
+15 %

with a very high amount once a year, 2,256 women aged 70 and over5

Muscle strength
30 trials

small effect on strength, none on mass or power1

  • Vitamin D3 (cholecalciferol) is a fat-soluble secosteroid. Liver and kidney turn it into the active form calcitriol, which acts on the vitamin D receptor.72
  • The active form mainly increases the absorption of calcium from the gut. A deficiency leads to bone loss, soft bones and weak muscles.2
  • In an analysis of 25 trials the odds of a respiratory infection fell by 12 percent, more with daily or weekly dosing, barely with large single amounts.3
  • The large VITAL trial with 25,871 people found no reduction in cancer or cardiovascular events. A very high amount once a year led to more falls and fractures in older women.45
  • Cholecalciferol is approved as a medicine. Everything here is the state of research, not a recommendation.7
Profile

Updated June 2026

Class
Fat-soluble secosteroid

Vitamin D

Use
Bone metabolism

immune function, muscle health

Half-life
~24 hours

active form calcitriol, D3 itself has longer storage

Status
Essential vitamin

non-prescription

Sizes
10ml/20000iu/ml

1 size in the shop

Contents 12 sections
  1. At a glance
  2. What is Vitamin D3?
  3. How it works
  4. Application and dosing
  5. What the research shows
  6. Research status
  7. Side effects
  8. Storage
  9. Related compounds
  10. FAQ
  11. Glossary
  12. Sources

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.

  1. Gut

    The active form increases calcium absorption from the gut2

    VDR
  2. Bone

    Deficiency leads to bone loss and fractures, a very high yearly amount to more fractures5

    Observed in trials
  3. Muscles

    Small effect on strength, larger with deficiency and from 651

    Observed in trials
  4. Airways

    12 percent lower odds of an acute respiratory infection3

    Observed in trials
  5. 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.

Vitamin D receptor
Gene
VDR
UniProt
P11473
ChEMBL
CHEMBL1977
Action
Agonist (ChEMBL), acts via the active form calcitriol
Glass liver, kidney and a bone side by side, small blue molecules travelling from the liver via the kidney to the bone
Liver and kidney turn vitamin D3 into the active form. Symbolic image.

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

All participants3
Vitamin D3 -12%
Daily or weekly3
Vitamin D3 -19%
With large single amounts3
Vitamin D3 -3%
Daily or weekly with severe deficiency3 baseline below 25 nmol/l
Vitamin D3 -70%

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

Cancer4
Vitamin D3 793%
Placebo 824%
Major cardiovascular event4
Vitamin D3 396%
Placebo 409%

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

Falls5
Vitamin D3, very high amount once a year 83.4%
Placebo 72.7%
Fractures5
Vitamin D3, very high amount once a year 4.9%
Placebo 3.9%

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.

Row of sealed test tubes in warm light, a small glowing glass disc like a sun at the end
Many large trials gave vitamin D3 by mouth. Symbolic image.

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

  1. Preclinical Biochemistry: calcium absorption via the active form
  2. Phase 1 no registered trial
  3. Phase 2 no registered trial
  4. Phase 3 3 trials, 2 completed
  5. Approval as a medicine (cholecalciferol)
84 participants in phase 3 Cholecalciferol is approved as a medicine, ChEMBL lists it at the highest stage 4. The trials test vitamin D3 in infections, cancer, heart, bones and muscles, some as an injection into the muscle.7
Show all 8 trials on a timelineHide timeline 7 completed 1 running 1 with results
Phase 3
Phase 4
Without phase

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.

Related

Related compounds

A different path: all in the TPD lexicon.

FAQ

Common questions about Vitamin D3

Short answers, each backed by the sources below.

Is vitamin D3 approved?

Yes, cholecalciferol is approved as a medicine, ChEMBL lists it at the highest stage 4 and as an agonist at the vitamin D receptor. The vial in the shop is a ready-made solution for injection, the regular entry describes giving it into the muscle or under the skin.7

How does vitamin D3 become active?

The liver turns vitamin D3 into the storage form 25-hydroxyvitamin D, the kidney turns that into active calcitriol. It acts on the vitamin D receptor and mainly increases calcium absorption from the gut. In deficiency parathyroid hormone rises and bone is broken down.27

Does vitamin D protect against respiratory infections?

An analysis of 25 trials with 10,933 participants found 12 percent lower odds of an acute respiratory infection. With daily or weekly dosing it was 19 percent, with severe deficiency 70 percent. With large single amounts there was no significant protection.3

Does vitamin D lower cancer or heart attacks?

Not in the VITAL trial with 25,871 people: over a median of 5.3 years there were 793 versus 824 cancer cases and 396 versus 409 major cardiovascular events, neither with a significant difference. Cancer deaths showed a trend that was not statistically significant.4

Does vitamin D help the muscles?

An analysis of 30 trials with 5,615 people found a small effect on muscle strength, none on muscle mass or muscle power. It was larger with low baseline levels and in people aged 65 and over.1

Do very high single amounts make sense?

The trials argue against it. In 2,256 women aged 70 and over a very high amount once a year led to 15 percent more falls and 26 percent more fractures than placebo, mostly in the first 3 months. Large single amounts did not work against respiratory infections either. A review explicitly names very high yearly amounts as possibly harmful.532

Glossary

Terms explained briefly

Dotted words in the text open these explanations directly.

25-hydroxyvitamin D
The storage form of vitamin D in the blood, the usual marker of vitamin D levels.
Calcitriol
The active hormone form of vitamin D, made in the kidney.
Cholecalciferol
The scientific name of vitamin D3, made in the skin by UV-B light.
Hypercalcaemia
Too much calcium in the blood, the typical result of a vitamin D overdose.
Intramuscular
Injected into the muscle, as opposed to subcutaneous, under the skin.
Meta-analysis
A joint analysis of several trials on the same question.
Odds ratio
The ratio of the odds of an event in two groups, similar to but not the same as risk.
Parathyroid hormone
Hormone of the parathyroid glands that rises in vitamin D deficiency and draws calcium from bone.
Secosteroid
A steroid with an opened ring in its backbone, which is how vitamin D is built.
Vitamin D receptor
A receptor in the cell nucleus through which calcitriol switches genes on or off.

Evidence

Sources

Show all 7 sourcesHide sources 5 Studies1 Trial registry1 Database checked 26 Oct 2026

Studies

  1. Vitamin D and muscle strength, meta-analysis of 30 trials

    Beaudart et al., Journal of Clinical Endocrinology and Metabolism, 2014

    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  2. Review: vitamin D, bone and osteoporosis

    Lips und van Schoor, Best Practice and Research Clinical Endocrinology and Metabolism, 2011

    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  3. Vitamin D against acute respiratory infections, individual participant data meta-analysis

    Martineau et al., BMJ, 2017

    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  4. VITAL: vitamin D3 against cancer and cardiovascular events

    Manson et al., New England Journal of Medicine, 2019

    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  5. Very high yearly amount of vitamin D3, falls and fractures

    Sanders et al., JAMA, 2010

    Checked 26 Oct 2026 via doi.org, Crossref, PubMed

Trial registry

  1. Trials with cholecalciferol on ClinicalTrials.gov

    ClinicalTrials.gov, U.S. National Library of Medicine

    Checked 26 Oct 2026 via ClinicalTrials.gov API v2

Database

  1. Cholecalciferol in ChEMBL (approved, vitamin D receptor)

    ChEMBL, EMBL-EBI (CHEMBL1042)

    Checked 26 Oct 2026 via ChEMBL

In the shop

Vitamin D3 in the catalog

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