Vitamin D3 (Cholecalciferol) is Strongly Preferred Over D2 (Ergocalciferol)
Cholecalciferol (D3) should be used for vitamin D supplementation due to its superior bioefficacy and longer duration of action compared to ergocalciferol (D2). 1
Key Reasons for D3 Superiority
Higher Potency and Sustained Levels
- D3 is approximately 3.2-fold more potent than D2 at raising serum 25(OH)D levels when using physiologic doses (≤25 μg/day), with D3 increasing levels by 4.8 nmol/L per 1 μg compared to only 1.5 nmol/L per 1 μg for D2 2
- D3 maintains serum 25(OH)D concentrations for significantly longer periods, with an elimination half-life of 82 days compared to only 33 days for D2 3
- When using intermittent dosing regimens (weekly or monthly), D3 is particularly advantageous as it produces more stable serum levels with less fluctuation 1, 2
Biochemical and Metabolic Advantages
- D3 is the natural form produced in human skin and found in animals, while D2 is derived from plants/fungi and is almost absent in the human diet 1
- D2 supplementation can actually decrease existing 25(OH)D3 levels - in one study, a 600,000 IU D2 mega-dose reduced 25(OH)D3 by an average of 4 ng/mL in 37 subjects 4
- D2 metabolites have diminished binding to vitamin D binding protein in plasma and undergo nonphysiologic metabolism with a shorter shelf life 5
Clinical Evidence Demonstrating D3 Superiority
Direct Comparison Studies
- In a head-to-head trial, a 10-day course of 500,000 IU D3 increased 25(OH)D levels by 47 ng/mL, while a single 600,000 IU D2 dose increased levels by only 10 ng/mL (P=3.15×10⁻¹⁸) 4
- Multiple randomized controlled trials consistently demonstrate that D3 is more effective than D2 at raising and maintaining serum 25(OH)D concentrations 3, 5
Recommended D3 Dosing Regimens
For Vitamin D Deficiency
- Initial treatment: 50,000 IU cholecalciferol (D3) weekly for 8-12 weeks 6, 7
- Maintenance therapy: 800-2,000 IU daily after the corrective phase 6, 7
- For severe deficiency (<15 ng/mL), use 50,000 IU weekly for 12 weeks followed by monthly maintenance 6, 7
For Prevention in Elderly
- A minimum of 800 IU daily of D3 is recommended for patients ≥65 years, even without baseline measurement 6, 7
Common Pitfall to Avoid
- Do not use D2 simply because it is available in prescription formulations - despite D2 being the form used in major prescription preparations in North America, the evidence clearly demonstrates D3 superiority 5
- Ensure adequate calcium intake alongside vitamin D supplementation 6, 7
- Use an assay that measures both 25(OH)D2 and 25(OH)D3 when monitoring vitamin D status, as the total represents the sum of both metabolites 1