Are vitamin D2 and vitamin D3 (cholecalciferol) interchangeable at a dose of 50,000 units?

Vitamin D2 vs D3 Interchangeability at 50,000 Units

No, vitamin D2 and vitamin D3 are not interchangeable at 50,000 units, as vitamin D3 (cholecalciferol) is approximately 87% more potent than vitamin D2 (ergocalciferol) in raising and maintaining serum 25-hydroxyvitamin D levels. 1

Comparative Efficacy of Vitamin D2 vs D3

Potency Differences

• Vitamin D3 is the preferred form due to higher bioefficacy compared to vitamin D2 2
• Research demonstrates that vitamin D3 is 87% more potent than vitamin D2 in raising and maintaining serum 25(OH)D concentrations 1
• Vitamin D3 produces 2-3 fold greater storage of vitamin D than equivalent doses of D2 1

Clinical Evidence

• A randomized controlled trial using 50,000 IU weekly dosing for 12 weeks showed:

  • D3 group achieved mean 25(OH)D increment of 45 ng/ml
  • D2 group achieved only 24 ng/ml increment
  • Area under the curve was significantly higher for D3 (2136 ng·d/ml) compared to D2 (1366 ng·d/ml) 1

• A more recent study (2022) found that injectable vitamin D3 was superior to injectable vitamin D2 for raising serum vitamin D levels, even though the vitamin D2 preparation contained double the molar units 3

Clinical Implications

Dosing Considerations

• For patients with severe malabsorption (such as after bariatric surgery), guidelines mention that "oral D2 or D3 may need to be as high as 50,000 units 1 to 3 times weekly to daily" 4
• However, given the potency differences, when choosing between the two forms:
  • A 50,000 IU dose of D2 would be roughly equivalent to 26,700 IU of D3
  • To achieve the same clinical effect as 50,000 IU of D3, approximately 93,500 IU of D2 would be needed

Safety Considerations

• Long-term supplementation with vitamin D3 in doses ranging from 5,000 to 50,000 IU/day appears to be safe in monitored settings 5
• No cases of vitamin D3-induced hypercalcemia were reported in patients receiving these high doses 5

Contradictory Evidence

It's important to note that some older research has suggested equivalence between D2 and D3:

• A 2008 study reported that 1,000 IU daily doses of D2 and D3 were equally effective in maintaining 25-hydroxyvitamin D status 6
• However, this finding has been contradicted by more recent and methodologically robust studies 1, 3

Practical Recommendations

When prescribing high-dose vitamin D supplementation:

1. Choose vitamin D3 (cholecalciferol) over D2 (ergocalciferol) whenever possible
2. If using D2 at 50,000 IU, be aware that it will not achieve the same serum levels as 50,000 IU of D3
3. Monitor 25(OH)D levels to ensure therapeutic targets are being reached
4. For patients with documented prior deficiency, supplementation can be initiated without waiting for new lab results 2

Common Pitfalls to Avoid

• Assuming D2 and D3 are equivalent on a unit-for-unit basis
• Failing to adjust dosing when switching between D2 and D3
• Not monitoring 25(OH)D levels after initiating high-dose supplementation
• Overlooking the need for adequate calcium intake (1000-1500 mg daily) alongside vitamin D supplementation 2