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Vitamin

Vitamin D3

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Vitamin D3. Steroid hormone precursor regulating ~5% of the human genome — bone, immune, and hormonal health.

How it works. Skin → cholecalciferol → liver (25-OH-D) → kidney (1,25-OH-D, calcitriol). Calcitriol binds VDR, heterodimerizes with RXR, and regulates transcription of ~1,000 genes.

What the research supports. 5 graded claims. Strongest: Reduces fracture risk in elderly (with calcium) (strong).

How much to take. Typical dose: 2,000–5,000 IU/day to maintain 40–60 ng/mL 25-OH-D. Morning or with largest meal.

Side effects and interactions. 3 medication interactions listed. Serious: Hypercalcemia (>10,000 IU/day chronic).

Stacking. Pairs well with Vitamin K2 (MK-7), Magnesium, Calcium. Avoid combining with High-dose calcium without K2.

Forms. 2 forms. Pick one to open its profile.

Key studies. 12 studies cited. The strongest are listed with links to PubMed.

Community. Experiences from people who have tried Vitamin D3. Anecdotes are not medical advice.

Vitamin D3. Steroid hormone precursor regulating ~5% of the human genome — bone, immune, and hormonal health.

Molecular structureC27H44O · 384.6 g/mol

What it is

A fat-soluble secosteroid synthesized in skin from UVB exposure and converted in the liver and kidneys to active calcitriol. Acts as a hormone via the vitamin D receptor (VDR) found in nearly every tissue.

Also called

Cholecalciferol

Food sources

Sunlight (UVB)Fatty fish (salmon, mackerel)Cod liver oilEgg yolksFortified dairy

Goals

Bone HealthImmune FunctionTestosterone SupportHormone OptimizationMood & AnxietyGeneral Wellness

How it works

Skin → cholecalciferol → liver (25-OH-D) → kidney (1,25-OH-D, calcitriol). Calcitriol binds VDR, heterodimerizes with RXR, and regulates transcription of ~1,000 genes.

Pathways

  • VDR/RXR gene transcription
  • Calcium absorption (TRPV6, calbindin)
  • Cathelicidin antimicrobial expression

Effects

  • ↑Calcium absorption increases
  • +Bone mineralization supports
  • +Immune defense supports
  • ↑Testosterone (in deficient men) increases
  • ↓PTH decreases
  • +Mood regulation supports

What the research supports

Reduces fracture risk in elderly (with calcium)strong
Reduces incidence of acute respiratory infectionsmoderate
Improves testosterone in deficient menmoderate
Reduces all-cause mortality (deficient cohorts)moderate
Reduces depression severity in deficient individualslimited

Strong: consistent results across large trials or meta-analyses. Moderate: several trials, mostly positive. Limited: small or mixed studies. Preclinical: animal or cell research only.

Typical dose
2,000–5,000 IU/day to maintain 40–60 ng/mL 25-OH-D
TimingMorning or with largest meal
With foodWith a meal containing fat
Best formD3 (cholecalciferol) in oil-based softgel
Upper limit4,000 IU/day (IOM UL); Endocrine Society allows up to 10,000
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Side effects & interactions

Common side effects

  • None at typical doses

Serious

  • Hypercalcemia (>10,000 IU/day chronic)
  • Kidney stones (high-dose without K2/Mg)

Medication interactions

Thiazide diureticsmoderate

Combined with high-dose D may cause hypercalcemia.

Digoxinmoderate

Vitamin D-induced hypercalcemia may potentiate digoxin toxicity.

Orlistat / bile-acid sequestrantsminor

Reduces absorption.

Check any supplement–medication combination with your pharmacist before starting.

Combines with

Pairs well

  • Vitamin K2 (MK-7)K2 directs absorbed calcium to bone rather than arteries.
  • MagnesiumRequired cofactor to convert D to its active form.
  • CalciumSynergistic for bone density.

Avoid combining

  • High-dose calcium without K2Risk of vascular calcification.

Key studies

12 studies cited in total.

Vitamin D supplementation and prevention of acute respiratory tract infections ↗
Meta-analysis · BMJ · 2017

Daily/weekly supplementation reduced ARI risk (aOR 0.81); strongest effect in deficient subjects (aOR 0.30).

Vitamin D3 vs D2 in raising 25(OH)D ↗
Meta-analysis · Am J Clin Nutr · 2012

D3 more effective at raising 25(OH)D.

PubMed: Vitamin D3 — Reduces fracture risk in elderly ↗
Systematic review · PubMed (NLM) · 2026

Opens current human and preclinical literature matching Vitamin D3 and "Reduces fracture risk in elderly". Filter by RCT, meta-analysis, or year on the results page.

Discussion

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