Vitamin D2 vs Vitamin D3: Efficacy and Dosage for Supplementation
Cholecalciferol (vitamin D3) is superior to ergocalciferol (vitamin D2) for vitamin D supplementation due to its greater bioefficacy, longer half-life, and better ability to sustain adequate 25(OH)D levels. 1, 2
Key Differences Between Vitamin D2 and D3
- Vitamin D3 (cholecalciferol) is the natural form found in animals and produced in human skin, while vitamin D2 (ergocalciferol) is primarily derived from plants and fungi 3
- Vitamin D3 has a longer plasma half-life (82 days vs 33 days for D2 after subtracting placebo values) and maintains higher 25(OH)D levels over time 4
- Vitamin D3 has higher binding affinity for vitamin D binding protein, hepatic vitamin D hydroxylase, and vitamin D receptors compared to vitamin D2 5
- Vitamin D3 is more stable during storage and more resistant to breakdown during cooking and baking than vitamin D2 1
Efficacy Differences
- In direct comparison studies, vitamin D3 produces approximately 28.6% higher area under the concentration curve (AUC) than equivalent doses of vitamin D2 4
- While both D2 and D3 can effectively raise 25(OH)D levels after loading doses, D3 is more effective at sustaining these levels long-term 4, 6
- Daily supplementation with 800 IU of vitamin D3 for 45 days produces significantly higher 25(OH)D levels than the same dose of vitamin D2 (22.9 ± 4.6 ng/ml vs 17.4 ± 5.5 ng/ml) 6
- Vitamin D3 is considered more potent per microgram dose than vitamin D2 1, 2
Dosage Recommendations
- For vitamin D deficiency, the recommended dosing is 50,000 IU of cholecalciferol (D3) weekly for 8-12 weeks followed by maintenance therapy of 800-2,000 IU daily 7
- For severe deficiency (<10-12 ng/mL), treatment with 50,000 IU cholecalciferol weekly for 12 weeks, followed by monthly maintenance is recommended 7
- For vitamin D insufficiency (20-30 ng/mL), treatment with 4,000 IU cholecalciferol daily for 12 weeks or 50,000 IU every other week for 12 weeks is recommended 7
- After achieving target levels (≥30 ng/mL), maintenance therapy with 800-2,000 IU daily or 50,000 IU monthly is recommended 7
- For elderly patients (≥65 years), a minimum of 800 IU daily of vitamin D3 is recommended even without baseline measurement 8, 7
Special Considerations
- Target serum 25(OH)D levels should be at least 30 ng/mL for optimal health benefits 3, 8, 7
- Monitoring of 25(OH)D levels should be performed after at least 3 months of supplementation to allow plateau levels to be reached 8
- For patients with chronic kidney disease, vitamin D supplementation is particularly important as kidney disease is a major risk factor for deficiency 3, 7
- The safer vitamin D sterol may be ergocalciferol rather than cholecalciferol for patients with chronic kidney disease, although this contradicts general recommendations 3
Common Pitfalls to Avoid
- Not ensuring adequate calcium intake (1,000-1,500 mg daily) alongside vitamin D supplementation 7
- Using single annual high doses which may lead to adverse outcomes 8
- Not accounting for individual variability in response to supplementation due to genetic factors, body composition, and environmental influences 7
- Using vitamin D2 for long-term supplementation when vitamin D3 would be more effective at maintaining adequate levels 2, 1
- Not using an assay that measures both 25(OH)D2 and 25(OH)D3 when monitoring vitamin D status 3