SYS ONLINE
SUPPLEMENT_SCHOLAR
evidence · mechanism · dose
Supplements/Vitamin

Vitamin D3

aka Cholecalciferol

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

Bone HealthImmune FunctionTestosterone SupportHormone OptimizationMood & AnxietyGeneral Wellness

Overview

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.

Natural sources
  • Sunlight (UVB)
  • Fatty fish (salmon, mackerel)
  • Cod liver oil
  • Egg yolks
  • Fortified dairy
Common forms
  • D3 cholecalciferol (preferred)
  • D2 ergocalciferol (less effective)
  • Calcifediol (rapid raise)

Forms & variants of Vitamin D3

Different chemical forms of Vitamin D3 behave differently. Browse each form's mechanism, bioavailability, and best-use context.

Maintenance 1000–2000 IU
Vitamin D3 (Maintenance)

Daily maintenance dose for non-deficient adults.

Repletion 5000–10000 IU
Vitamin D3 (Repletion)

Repletion dose for deficiency under medical supervision.

Mechanism of action

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
Receptors
  • · Vitamin D Receptor (VDR)
Hormones
  • · Testosterone (supports)
  • · PTH (suppresses)
  • · Insulin

Effects on the body

Increases
Calcium absorption
Supports
Bone mineralization
Supports
Immune defense
Increases
Testosterone (in deficient men)
Decreases
PTH
Supports
Mood regulation

Organ system effects

Bones

Drives intestinal Ca/P absorption; required for mineralization.

Immune System

Upregulates cathelicidin and defensins; modulates T-reg activity.

Endocrine

Correlates with serum testosterone in deficient men.

Brain & CNS

VDR expressed in hippocampus; deficiency linked to depression.

Skeletal Muscle

Required for type-II fiber strength; deficiency causes myopathy.

Evidence-based benefits

Reduces fracture risk in elderly (with calcium)

Strong evidence

Reduces incidence of acute respiratory infections

Moderate evidence

Improves testosterone in deficient men

Moderate evidence

Reduces depression severity in deficient individuals

Limited evidence

Reduces all-cause mortality (deficient cohorts)

Moderate evidence

Potential side effects

Common
  • · None at typical doses
Rare
  • · Nausea
  • · Constipation
  • · Metallic taste
Serious
  • · Hypercalcemia (>10,000 IU/day chronic)
  • · Kidney stones (high-dose without K2/Mg)

Drug interactions

Thiazide diuretics
Combined with high-dose D may cause hypercalcemia.
moderate
Digoxin
Vitamin D-induced hypercalcemia may potentiate digoxin toxicity.
moderate
Orlistat / bile-acid sequestrants
Reduces absorption.
minor

Safety & non-supplemental interactions

Educational summary — always confirm with your clinician or pharmacist before starting, stopping, or combining with prescription therapy.

Avoid with these conditions
  • ·Hormone-sensitive cancers (breast, prostate, ovarian, uterine)
  • ·Autoimmune disease (theoretical immune activation)
  • ·Hypercalcemia
  • ·Sarcoidosis, tuberculosis, lymphoma (granulomatous — extra 1,25-OH activation)
  • ·Primary hyperparathyroidism
  • ·Kidney stones (calcium-oxalate)
Avoid / monitor with these medications
  • ·Hormonal contraceptives, HRT, tamoxifen, aromatase inhibitors
  • ·Immunosuppressants
  • ·Thiazide diuretics (hypercalcemia)
  • ·Digoxin (arrhythmia risk with high calcium)
  • ·Steroids (reduce vitamin D action)
  • ·Orlistat, cholestyramine, mineral oil (reduced absorption)

Supplement interactions

Pairs well with
  • Vitamin K2 (MK-7)
    K2 directs absorbed calcium to bone rather than arteries.
  • Magnesium
    Required cofactor to convert D to its active form.
  • Calcium
    Synergistic for bone density.
Avoid combining with
  • High-dose calcium without K2
    Risk of vascular calcification.

Dosing & bioavailability

Typical dose
2,000–5,000 IU/day to maintain 40–60 ng/mL 25-OH-D
Beginner dose
1,000 IU
Study range
1,000–10,000 IU/day
Upper safe limit
4,000 IU/day (IOM UL); Endocrine Society allows up to 10,000
Best form
D3 (cholecalciferol) in oil-based softgel
Timing
Morning or with largest meal
With food?
With a meal containing fat
Absorption
Fat-soluble — absorption ~30% higher with a fatty meal

Where to buy

Affiliate-style search links to reputable retailers. We don't endorse specific brands — verify third-party testing (USP, NSF, Informed Sport) before purchase.

Vitamin
Vitamin D3
Amazon
Wide selection · fast shipping
Vitamin
Vitamin D3
iHerb
Global delivery · curated brands
Vitamin
Vitamin D3
Thorne
Practitioner-grade · NSF tested

Scientific evidence (12)

Meta-analysisBMJ · 2017

Vitamin D supplementation and prevention of acute respiratory tract infections

Martineau AR, et al.

Individual participant data meta-analysis of 25 RCTs, n=10,933.

Key findings

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

Open study
Meta-analysisAm J Clin Nutr · 2012

Vitamin D3 vs D2 in raising 25(OH)D

Tripkovic L, et al.

Meta-analysis of D2 vs D3 supplementation.

Key findings

D3 more effective at raising 25(OH)D.

Open study
Systematic reviewPubMed (NLM) · 1970

PubMed: Vitamin D3 — Reduces fracture risk in elderly

Live PubMed search

Live results for "Vitamin D3 Reduces fracture risk in elderly" across the PubMed/MEDLINE peer-reviewed index.

Key findings

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.

Open study
Systematic reviewPubMed (NLM) · 1970

PubMed: Vitamin D3 — Reduces incidence of acute respiratory infections

Live PubMed search

Live results for "Vitamin D3 Reduces incidence of acute respiratory infections" across the PubMed/MEDLINE peer-reviewed index.

Key findings

Opens current human and preclinical literature matching Vitamin D3 and "Reduces incidence of acute respiratory infections". Filter by RCT, meta-analysis, or year on the results page.

Open study
Systematic reviewPubMed (NLM) · 1970

PubMed: Vitamin D3 — Improves testosterone in deficient men

Live PubMed search

Live results for "Vitamin D3 Improves testosterone in deficient men" across the PubMed/MEDLINE peer-reviewed index.

Key findings

Opens current human and preclinical literature matching Vitamin D3 and "Improves testosterone in deficient men". Filter by RCT, meta-analysis, or year on the results page.

Open study
Systematic reviewPubMed (NLM) · 1970

PubMed: Vitamin D3 — Reduces depression severity in deficient individuals

Live PubMed search

Live results for "Vitamin D3 Reduces depression severity in deficient individuals" across the PubMed/MEDLINE peer-reviewed index.

Key findings

Opens current human and preclinical literature matching Vitamin D3 and "Reduces depression severity in deficient individuals". Filter by RCT, meta-analysis, or year on the results page.

Open study
Systematic reviewPubMed (NLM) · 1970

PubMed: Vitamin D3 — randomized controlled trial

Live PubMed search

Live results for "Vitamin D3 randomized controlled trial" across the PubMed/MEDLINE peer-reviewed index.

Key findings

Opens current human and preclinical literature matching Vitamin D3 and "randomized controlled trial". Filter by RCT, meta-analysis, or year on the results page.

Open study
Systematic reviewPubMed (NLM) · 1970

PubMed: Vitamin D3 — meta-analysis

Live PubMed search

Live results for "Vitamin D3 meta-analysis" across the PubMed/MEDLINE peer-reviewed index.

Key findings

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

Open study
Systematic reviewPubMed (NLM) · 1970

PubMed: Vitamin D3 — pharmacokinetics

Live PubMed search

Live results for "Vitamin D3 pharmacokinetics" across the PubMed/MEDLINE peer-reviewed index.

Key findings

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

Open study
Systematic reviewPubMed (NLM) · 1970

PubMed: Vitamin D3 — safety adverse events

Live PubMed search

Live results for "Vitamin D3 safety adverse events" across the PubMed/MEDLINE peer-reviewed index.

Key findings

Opens current human and preclinical literature matching Vitamin D3 and "safety adverse events". Filter by RCT, meta-analysis, or year on the results page.

Open study
Systematic reviewPubMed (NLM) · 1970

PubMed: Vitamin D3 — dose response

Live PubMed search

Live results for "Vitamin D3 dose response" across the PubMed/MEDLINE peer-reviewed index.

Key findings

Opens current human and preclinical literature matching Vitamin D3 and "dose response". Filter by RCT, meta-analysis, or year on the results page.

Open study
Systematic reviewGoogle Scholar · 1970

Google Scholar: Vitamin D3 — clinical evidence

Live Scholar search

Cross-database citation index for Vitamin D3 as it relates to "clinical evidence".

Key findings

Includes preprints, theses, and journal articles. Useful for tracking citation counts and follow-on work.

Open study
Educational use only. This profile is not medical advice. Consult a qualified healthcare professional before starting any supplement, especially if you take prescription medication or have a chronic condition.