What is the difference between vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol) supplementation?

Vitamin D2 vs D3 Supplementation: Key Differences

Vitamin D3 (cholecalciferol) is more effective than vitamin D2 (ergocalciferol) at raising and maintaining serum 25-hydroxyvitamin D levels, particularly when using longer dosing intervals. 1

Metabolic Differences

• Source differences:

  • D2 (ergocalciferol): Plant/mushroom-derived form 1
  • D3 (cholecalciferol): Animal-derived form, also produced in human skin upon sun exposure 1

• Potency differences:

  • D3 is approximately 3.2 times more potent than D2 when using physiologic doses 2
  • For each 1 μg of supplement: D3 raises serum 25OHD by 1.5 ± 0.9 nmol/L, while D3 raises it by 4.8 ± 1.2 nmol/L 2

Clinical Effectiveness

• Raising serum 25OHD levels:

  • With daily dosing: Both forms are similarly effective 1
  • With intermittent dosing: D3 maintains levels for longer periods 1, 3
  • D3 produces more stable serum levels with intermittent dosing 2

• Half-life differences:

  • D3 has a longer elimination half-life (82 days) compared to D2 (33 days) 3
  • This explains why D3 is superior for maintaining vitamin D status over time 4

Binding and Metabolism

• Protein binding: D2 metabolites bind less effectively to vitamin D binding protein in plasma 4
• Absorption: Calcifediol (25OHD3) has higher intestinal absorption than either D2 or D3, which may be advantageous in malabsorptive conditions 2

Clinical Application

• Daily supplementation:

  • For daily dosing, either form can be used, though D3 is preferred 1
  • Recommended daily intake: 800-1000 IU for adults over 50 years 1

• Intermittent dosing:

  • D3 is clearly superior for weekly or monthly dosing regimens 3
  • For correcting deficiency with weekly dosing, D3 maintains levels better 5

Special Populations

• For patients with chronic kidney disease:
  • Both D2 and D3 can be used to correct vitamin D deficiency 1
  • Some guidelines suggest D2 may be safer in certain kidney conditions, though comparative trials in humans are lacking 1

Practical Considerations

• D3 has a longer shelf life than D2 4
• D3 demonstrates a more linear dose-response curve regardless of baseline levels 2
• When using 800 IU daily supplementation, D3 produces higher 25OHD levels than D2 after 45 days of treatment 5

In conclusion, while both forms can effectively raise vitamin D levels with daily dosing, vitamin D3 is the preferred form for most clinical applications due to its superior pharmacokinetics, especially when using intermittent dosing regimens or when treating significant deficiency.