What are the different types of vitamin D (Vitamin D) and their effects on the body?

Types of Vitamin D and Their Physiological Effects

Vitamin D exists in six distinct forms with varying biological activities: three endogenous forms derived from cholesterol (cholecalciferol/D3, calcidiol/25(OH)D3, and calcitriol/1,25(OH)2D3) and three plant-derived forms (ergocalciferol/D2 and its corresponding hydroxylated metabolites). 1

Primary Forms of Vitamin D

Endogenous (Animal-Derived) Forms

• Cholecalciferol (Vitamin D3): The precursor form synthesized in skin from 7-dehydrocholesterol upon exposure to ultraviolet B radiation, or obtained from animal food sources (fatty fish, eggs, liver) 1

  • This is the biologically inert precursor that requires activation through sequential hydroxylation 1, 2
  • Sun exposure of face and arms for 15 minutes per week can produce tens of thousands of units in light-skinned individuals 1
  • Endogenously synthesized D3 is carried by vitamin D-binding protein (DBP), which may result in distinct biodistribution compared to supplemental forms 1

• Calcidiol [25-hydroxyvitamin D or 25(OH)D3]: The monohydroxylated form produced in the liver, which has partial biological activity 1

  • This is the longer-lasting metabolite used clinically to diagnose vitamin D deficiency, not the more active form 1
  • Serum 25(OH)D levels above 50 nmol/L (20 ng/mL) are considered adequate, though levels above 50 ng/mL may be necessary for optimal health benefits 1, 3
  • Levels of 25(OH)D3 tend to vary inversely with the active form, possibly due to displacement from D-binding protein 1

• Calcitriol [1,25-dihydroxyvitamin D or 1,25(OH)2D3]: The fully hydroxylated "active" form produced in the kidneys, which is the most biologically potent 1

  • This is the hormonal form that binds to vitamin D receptors (VDRs) present in nearly all body tissues 1, 4
  • Once bound to VDRs, the complex translocates to the nucleus and regulates expression of over 1200 genes 3
  • Calcitriol is necessary for maintaining serum-ionized calcium in advanced renal failure and hypoparathyroidism, but is ineffective for most other conditions including infections and routine vitamin D replacement 3

Exogenous (Plant-Derived) Forms

• Ergocalciferol (Vitamin D2): The plant-derived form consumed primarily through diet (fatty fish, fortified foods like milk, yogurt, orange juice) 1
  • D2 also has corresponding monohydroxy [25(OH)D2] and dihydroxy [1,25(OH)2D2] metabolites with similar but not identical activity to D3 forms 1
  • Dietary or supplemental D2 taken orally is absorbed differently than endogenous D3, being carried within lipoprotein particles rather than by DBP 1

Functional Differences and Clinical Implications

Activation Pathway

Both D2 and D3 are biologically inert when obtained and must undergo sequential hydroxylation: first in the liver (producing 25(OH)D) and then in the kidneys (producing 1,25(OH)2D) before becoming biologically active 1, 2, 3

Physiological Actions

• Classic skeletal effects: Vitamin D controls calcium absorption in the small intestines, interacts with parathyroid hormone to maintain calcium homeostasis, and is essential for bone growth and maintaining bone density 1

  • Insufficient vitamin D leads to inadequate calcitriol levels, impairing dietary calcium absorption and forcing the body to use calcium from skeletal stores, weakening bones 1
  • Deficiency causes rickets in children and osteomalacia in adults 1, 2, 4

• Non-classic effects: The vitamin D receptor is expressed in skeletal muscle, cardiac muscle, bone, immune system, skin, and endocrine organs 1

  • Stimulation of skeletal muscle receptors promotes protein synthesis, improving muscle strength and balance 1
  • Vitamin D regulates hundreds of genes affecting immune function, cardiovascular health, and metabolic processes 1, 3, 4

Clinical Measurement and Supplementation

For routine assessment and supplementation, cholecalciferol (D3) should be used to correct deficiency and raise serum 25(OH)D to target concentrations 3

• Calcidiol [25(OH)D] raises serum levels rapidly and is the agent of choice in emergencies such as infections, ICU patients, and insufficient hepatic 25-hydroxylase activity 3
• Calcitriol has a narrow therapeutic margin and should be reserved specifically for advanced renal failure and hypoparathyroidism, not for routine supplementation, osteoporosis, or infections 3
• 1α-vitamin D analogs should not be used for routine conditions due to high costs and higher incidence of adverse effects 3

Dosing Recommendations

• Recommended daily oral intake ranges from 600-800 IU for general adults 1, 5
• Patients at risk for deficiency may require 1500-4000 IU daily 1
• The general upper daily limit is 4000 IU, though up to 10,000 IU may be appropriate for high-risk patients 1
• High-potency formulations (50,000 IU cholecalciferol) are available for weekly dosing in deficiency states 6

Important Caveats

Vitamin D is technically a misnomer—it functions as a steroid hormone, not a true vitamin, since the body can synthesize it endogenously 1

• As a fat-soluble hormone, vitamin D requires special transport mechanisms in blood: endogenous forms use DBP while dietary forms use lipoprotein particles, potentially affecting tissue distribution 1
• Excess vitamin D can cause calcific vasculopathy and has been used experimentally to induce vascular calcification in animal models 1
• The cardiovascular effects are complex and biphasic, with both beneficial and toxic effects possible 1
• Vitamin D interacts with vitamin A to modulate immune response and gene regulation 1