What is the recommended choice between Vitamin D2 (ergocalciferol) and Vitamin D3 (cholecalciferol) for supplementation?

Vitamin D3 (Cholecalciferol) is Superior to Vitamin D2 (Ergocalciferol) for Supplementation

For most patients requiring vitamin D supplementation, vitamin D3 (cholecalciferol) should be preferred over vitamin D2 (ergocalciferol) due to its superior pharmacokinetic profile and ability to maintain serum 25(OH)D levels for longer periods, particularly when using intermittent dosing regimens. 1

Comparative Effectiveness of Vitamin D2 vs D3

Pharmacokinetic Differences

• Vitamin D3 maintains serum 25(OH)D concentrations for a longer period compared to vitamin D2, especially when using intermittent dosing regimens 1
• Vitamin D2 has:
  • Shorter plasma half-life
  • Lower affinity for vitamin D binding protein
  • Lower affinity for hepatic vitamin D hydroxylase
  • Lower affinity for vitamin D receptor 2

Dosing Equivalence

• When using daily dosing, both forms can effectively raise 25(OH)D levels, though vitamin D3 is still more potent 1
• For intermittent dosing (weekly, monthly), vitamin D3 provides more stable serum levels with less fluctuation 3
• Vitamin D3 is approximately 3-5 times more potent than vitamin D2 when comparing equivalent doses 3, 2

Clinical Recommendations

General Population

• For routine supplementation, use vitamin D3 (cholecalciferol) at doses of:
  • 800-1000 IU daily for adults over 50 years 1
  • 400 IU daily for younger adults 1
  • Target serum 25(OH)D level: 30-40 ng/mL (75-100 nmol/L) 1

Special Populations

• For patients with malabsorption syndromes (e.g., celiac disease):

  • Vitamin D3 is still preferred due to better absorption characteristics 1
  • Higher doses may be required to achieve target levels 1

• For patients with chronic kidney disease:

  • Either form can be used for prevention of vitamin D deficiency 1
  • For treatment of established deficiency, ergocalciferol (D2) has been traditionally used in high doses (50,000 IU weekly for 8-12 weeks) 1

Monitoring

• Check 25(OH)D levels after at least 3 months of supplementation 1
• Use an assay that measures both 25(OH)D2 and 25(OH)D3 1

Special Considerations

Safety

• Both forms are generally safe at recommended doses
• Upper safety limit for 25(OH)D is 100 ng/mL 1
• Vitamin D toxicity is rare but can occur with daily doses exceeding 50,000 IU that produce 25(OH)D levels >150 ng/mL 1

Practical Aspects

• Vitamin D3 is more widely available in over-the-counter supplements
• For strict vegetarians/vegans who prefer plant-sourced supplements, vitamin D2 (derived from plants) may be preferred despite its lower potency 1
• In countries where only one form is available, that form should be used rather than avoiding supplementation altogether

Common Pitfalls to Avoid

• Failing to recognize that intermittent high-dose vitamin D2 is less effective than equivalent vitamin D3 dosing
• Not accounting for the 3-5 fold potency difference when switching between forms
• Using calcitriol or other 1-hydroxylated vitamin D sterols to treat vitamin D deficiency (these should be avoided) 1
• Neglecting to monitor 25(OH)D levels after starting supplementation, especially in high-risk individuals

The evidence strongly supports vitamin D3 as the preferred form for supplementation in most clinical scenarios, with vitamin D2 being a reasonable alternative when D3 is unavailable or unacceptable to the patient for ethical/religious reasons.