§.01Two different molecules.
D2 (ergocalciferol) is plant-derived, made by UV irradiation of yeast or mushroom sterol. Used as the high-dose prescription form in the US (50,000 IU capsules, weekly dosing for short repletion protocols).
D3 (cholecalciferol) is the form your skin synthesizes from UVB exposure. It is also available from lanolin (sheep's wool) or lichen (vegan). Used in essentially all OTC daily-dose supplements.
Both raise serum 25(OH)D, but not equally. D3 is more efficient per IU and maintains levels longer (Tripkovic et al., 2012).
§.02Why your prescription is D2.
The US prescription supply chain is set up around D2 because:
- D2 was historically the established prescription-grade form (cheaper to mass-produce decades ago).
- Insurance reimbursement structures are tied to the D2 NDC codes.
- The 50,000 IU dosage is convenient for once-weekly repletion protocols.
None of these are reasons D2 is biologically superior. D3 at equivalent doses outperforms D2 in raising 25(OH)D, but D3 is not as widely available as a high-dose prescription product in the US.
§.03When D2 is the right choice.
- Your endocrinologist prescribed it for a specific repletion protocol. Follow the prescription; the dosage is calibrated.
- You require strict vegan sourcing and your D3 access is limited. (Lichen-derived D3 is widely available now, so this is rare.)
- Insurance covers D2 but not D3 and cost matters more than the modest efficacy gap.
§.04When D3 is the right choice (most people).
- Daily supplementation for general health.
- Maintenance after a prescription D2 repletion protocol ends.
- Anyone choosing their own OTC supplement.
- Pregnancy (with prescriber input).
- Pediatric supplementation (with pediatrician guidance).
§.05Switching from prescription D2 to maintenance D3.
If your clinician prescribed 8 to 12 weeks of weekly 50,000 IU D2 for documented deficiency, you should typically transition to daily D3 for maintenance after the prescribed course. Common transition:
- Complete the D2 prescription course.
- Get a follow-up 25(OH)D blood test.
- If level is in the 30-50 ng/mL range, switch to 1,000 to 2,000 IU D3 daily.
- Re-check at 3-6 months to confirm stability.
This is the standard repletion-then-maintenance protocol. Always coordinate with your prescriber, especially if you have malabsorption or chronic disease.
§.99The bottom line.
For over-the-counter daily supplementation, take D3 (cholecalciferol). It is more bioavailable, raises and maintains serum 25(OH)D more efficiently, and works at lower doses. D2 (ergocalciferol) is the prescription form (typically 50,000 IU weekly for short-term repletion) and is used because it is the available high-dose prescription option. If your clinician prescribed D2 for a specific repletion protocol, take it as prescribed. For ongoing maintenance, transition to D3.
Vitamin D3 2,000 IU, 90 softgels — at the apothecary.
Reviewed by Dr. Marthe Janssen, PharmD. Last updated May 19, 2026.
Disclaimer: this article is educational and does not substitute for advice from your prescriber. Statements have not been evaluated by the FDA. This product is not intended to diagnose, treat, cure, or prevent any disease.