What Are Vitamin D2 and D3?
Vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol) are the two forms of vitamin D available for supplementation, with D2 derived from plant/fungal sources and D3 from animal sources or synthesized in human skin upon sun exposure. 1, 2, 1
Sources and Origin
Vitamin D2 (Ergocalciferol):
- Obtained from plant and fungal sources, particularly mushrooms 2
- Almost absent in the typical diet unless specifically fortified 2
- Suitable for vegetarians and those with dietary restrictions against animal products 3
Vitamin D3 (Cholecalciferol):
- Synthesized endogenously in human skin when exposed to ultraviolet B radiation from sunlight 1
- Found naturally in dietary sources, primarily fatty fish 1
- Also present in fortified foods such as milk, yogurt, and orange juice 1
- The form naturally produced by the human body 3
Biological Activity and Metabolism
Both forms undergo similar metabolic pathways but with important differences:
- Both are biologically inactive until hydroxylated in the liver to form 25-hydroxyvitamin D (calcidiol), then further activated in the kidneys to 1,25-dihydroxyvitamin D (calcitriol) 1
- Vitamin D3 demonstrates superior potency and efficacy in raising serum 25(OH)D levels compared to D2 3
- D2 has a shorter plasma half-life and lower affinity for vitamin D binding protein 4, 5
- D2 absorption can be erratic, particularly in patients with malabsorption conditions 3
Clinical Effectiveness: D3 is Superior
The evidence strongly favors vitamin D3 over D2 for supplementation. A 2009 randomized controlled trial in adults showed that 50,000 IU weekly of cholecalciferol produced greater increases in serum 25(OH)D than equivalent doses of ergocalciferol, with 100% of D3-treated subjects achieving target levels versus only 60% with D2 3.
Key Differences in Efficacy:
- D3 more effectively produces sustained rises in serum 25(OH)D 3
- D2 has demonstrated failure to treat vitamin D deficiency effectively even at high doses 3
- D3 maintains serum levels longer when given intermittently 2
- Most osteoporosis trials have used cholecalciferol, not ergocalciferol 3
Clinical Recommendations
Vitamin D3 (cholecalciferol) should be the preferred form for supplementation 3. The Cystic Fibrosis Foundation provides a Grade B recommendation for D3 over D2 3.
When D2 May Be Considered:
- Vegetarians or individuals with dietary restrictions prohibiting animal products 3
- Important caveat: Higher doses of D2 may be required to achieve equivalent effects 3
- If D2 effectively maintains serum 25(OH)D ≥30 ng/mL, continuation may be acceptable rather than switching 3
Laboratory Testing Considerations
When monitoring vitamin D status, use assays that measure both 25(OH)D2 and 25(OH)D3 3, 2. This is critical because:
- Some assays do not measure both forms with equal sensitivity 3
- In countries where both forms are available for supplementation, failing to measure both can lead to inaccurate assessment 2
- Serum concentrations can vary by up to 30% between laboratories 3
Formulations Available
Vitamin D2: Available as ergocalciferol in liquid form (8000 IU/mL in propylene glycol) 6
Vitamin D3: Available as cholecalciferol in softgel capsules (commonly 50,000 IU with soybean oil, glycerin, and gelatin) 7