| Parameter | Ergocalciferol (Vitamin D₂) | Cholecalciferol (Vitamin D₃) |
|---|---|---|
| Chemical name | Ergocalciferol | Cholecalciferol |
| Vitamin D form | D₂ | D₃ |
| Source | Plant/fungal (UV-irradiated ergosterol) | Animal-derived; endogenous skin synthesis |
| FDA status | Approved | Approved |
| Common formulations | Rx high-dose (e.g., 50,000 IU capsules) | OTC and Rx (400–10,000 IU; high-dose available) |
| Potency (25-OH-D increase) | Lower | Higher (≈1.7–2× D₂) |
| Half-life of 25-OH-D | Shorter | Longer |
| Binding to vitamin D–binding protein | Lower affinity | Higher affinity |
| Metabolism | Hepatic 25-hydroxylation → renal 1α-hydroxylation | Same pathway |
| Effect on PTH suppression | Less sustained | More sustained |
| Clinical efficacy | Inferior for long-term repletion | Preferred for maintenance and repletion |
| Use in deficiency | Historically used; less favored | First-line in most guidelines |
| Stability | Less stable | More stable |
| Special populations | May be used for strict vegan patients | Preferred unless contraindicated |
| Interchangeability | Not bioequivalent to D₃ | Not bioequivalent to D₂ |
Key Clinical Pearls
- D₃ is preferred for both repletion and maintenance due to superior pharmacokinetics and sustained serum 25-OH-D levels.
- D₂ 50,000 IU weekly remains common in legacy protocols but may require closer monitoring.
- Switching from D₂ → D₃ often results in improved vitamin D status at equivalent IU dosing.
Conversion strategies (D₂ → D₃)
Below is a clinically practical guide for converting ergocalciferol (D₂) to cholecalciferol (D₃), written for a clinical pharmacist.
Why Convert D₂ → D₃?- D₃ has greater potency and longer half-life
- Produces more sustained 25-OH-vitamin D levels
- Preferred by most clinical guidelines
- Reduces variability in response
Dose Conversion Principles
- IU ≠ IU clinically
- D₃ is approximately 1.7–2× more potent than D₂ in raising serum 25-OH-D
- Conversion should consider:
- Baseline 25-OH-D
- Duration of therapy
- Risk of hypercalcemia
- Adherence
Practical Conversion Table
| Current Ergocalciferol (D₂) Regimen | Suggested Cholecalciferol (D₃) Conversion | Clinical Notes |
|---|---|---|
| 50,000 IU weekly | 25,000–30,000 IU weekly or 4,000–5,000 IU daily | Most common conversion |
| 50,000 IU every 2 weeks | 10,000–15,000 IU weekly | Suitable for maintenance |
| 50,000 IU monthly | 2,000 IU daily | Mild deficiency/maintenance |
| 1,000 IU daily | 800–1,000 IU daily | Often equivalent clinically |
| 2,000 IU daily | 1,000–1,500 IU daily | Adjust per serum level |
Suggested Conversion Algorithm
- Complete current D₂ loading phase (if mid-course)
- Switch to D₃ maintenance or repletion
- Use ~50–60% of the D₂ IU dose
- Recheck 25-OH-D in 8–12 weeks
- Adjust dose to target:
- General population: ≥30 ng/mL (75 nmol/L)
- High-risk patients: 30–50 ng/mL
Special Clinical Populations
| Population | Recommendation |
|---|---|
| Obesity | May require 1.5–2× higher D₃ dose |
| Malabsorption | Consider daily dosing or higher doses |
| CKD (non-dialysis) | D₃ acceptable if 1-α hydroxylation intact |
| Dialysis | Use active vitamin D analogs instead |
| Vegan patients | D₂ or plant-derived D₃ acceptable |
Monitoring & Safety
- Check Ca²⁺, PO₄³⁻, PTH if high-dose or long-term
- Avoid chronic D₃ doses > 10,000 IU/day without monitoring
- Watch for hypercalcemia (rare but dose-related)