What is the preferred form of vitamin D for supplementation, vitamin D2 (ergocalciferol) or vitamin D3 (cholecalciferol)?

Vitamin D3 (Cholecalciferol) is Preferred Over Vitamin D2 (Ergocalciferol) for Supplementation

Vitamin D3 (cholecalciferol) is the preferred form of vitamin D supplementation over vitamin D2 (ergocalciferol) due to its higher bioefficacy, better pharmacokinetic properties, and superior ability to sustain serum 25(OH)D levels. 1

Evidence Supporting Vitamin D3 Superiority

Pharmacokinetic Advantages

• Vitamin D3 produces more sustained increases in serum 25(OH)D levels compared to vitamin D2 1
• Vitamin D3 is approximately 87% more potent in raising and maintaining serum 25(OH)D concentrations 2
• The elimination half-life of 25(OH)D is longer with D3 supplementation (82 days) compared to D2 (33 days) 3

Clinical Efficacy

• Meta-analysis data shows vitamin D3 is more efficacious than vitamin D2 in improving vitamin D status and regulating parathyroid hormone levels, regardless of participant demographics, dosage, or vehicle of supplementation 4
• When comparing equal doses, vitamin D3 results in approximately 28.6% higher area under the concentration-time curve than vitamin D2 3
• European cystic fibrosis guidelines specifically state that vitamin D3 is preferred over D2 for supplementation 5

Dosing Considerations

Standard Dosing Regimens

• For vitamin D deficiency (<20 ng/mL), the following vitamin D3 regimens are recommended:
  • Severe deficiency (<5 ng/mL): 50,000 IU weekly for 8-12 weeks, then maintenance 1
  • Mild deficiency (5-15 ng/mL): 8,000 IU daily for 4 weeks, then 4,000 IU daily for 2 months 1
  • Insufficiency (16-30 ng/mL): 4,000 IU daily for 12 weeks or 50,000 IU every other week for 12 weeks 1

Maintenance Therapy

• Maintenance therapy with vitamin D3 can be 2,000 IU daily or 50,000 IU every 4 weeks 1
• The FDA-approved vitamin D3 supplement is available as 50,000 IU softgel capsules with a recommended dosage of one capsule weekly or as directed by a physician 6

Monitoring and Safety

• Serum 25(OH)D levels should be checked after 3 months of supplementation 1
• Target 25(OH)D level is ≥30 ng/mL (75 nmol/L) for optimal health 1, though some guidelines accept a minimum threshold of 20 ng/mL (50 nmol/L) 5
• Annual monitoring of 25(OH)D levels is recommended, preferably at the end of darker months 5
• Recheck levels 3-6 months after a dosage change 5

Special Considerations

• Vitamin D3 has greater potency for storage in body fat compared to vitamin D2 2
• Patients with malabsorption syndromes may require higher doses of vitamin D3 1
• The linear dose-response curve of calcifediol (25(OH)D3) may offer advantages over both vitamin D2 and D3 in certain clinical scenarios, though this is a different supplement option altogether 7

Cautions and Contraindications

• Vitamin D3 supplementation is contraindicated in patients with hypercalcemia, malabsorption syndrome, abnormal sensitivity to vitamin D, and hypervitaminosis D 6
• High-dose vitamin D3 is not recommended for children, pregnant or lactating women, or individuals with liver disease without medical supervision 6
• Individuals taking thiazide diuretics may be at greater risk of toxicity 6

The evidence consistently demonstrates that vitamin D3 is the superior form for supplementation, with greater potency, better bioavailability, and more sustained effects on serum 25(OH)D levels compared to vitamin D2.