What is the difference between cholecalciferol (Vitamin D3) and ergocalciferol (Vitamin D2)?

Differences Between Cholecalciferol (Vitamin D3) and Ergocalciferol (Vitamin D2)

Cholecalciferol (vitamin D3) has higher bioefficacy than ergocalciferol (vitamin D2) for raising serum vitamin D levels and should be preferred when treating vitamin D deficiency. 1

Chemical and Source Differences

• Origin:

  • Cholecalciferol (D3): Animal-derived, endogenously produced in human skin upon exposure to sunlight
  • Ergocalciferol (D2): Plant-derived, produced by UV irradiation of ergosterol from yeast and fungi 1

• Chemical Structure:

  • Both are secosteroids (steroid hormones)
  • D3 is 9,10-secocholesta-5,7,10(19)-trien-3beta-ol
  • D2 differs from D3 in its side chain structure 1

Efficacy Differences

Superior Efficacy of Vitamin D3

• Cholecalciferol (D3) is more effective than ergocalciferol (D2) at:

  • Raising total 25(OH)D levels (mean difference: 15.69 nmol/L higher with D3) 2
  • Regulating parathyroid hormone (PTH) levels 2
  • Maintaining sustained serum vitamin D levels 3

• In CKD patients, cholecalciferol produced increases in 25(OH)D that were more than twice as great as those from ergocalciferol when standardized to the same dosage (2.7 ± 0.3 ng/ml vs 1.1 ± 0.3 ng/ml) 4

• In a study of Thai female healthcare workers, daily cholecalciferol supplementation resulted in significantly greater increases in serum 25(OH)D levels compared to weekly ergocalciferol (8.41 ng/mL vs 4.76 ng/mL increase at 6 months) 5

Factors Affecting Differential Response

• The difference in efficacy between D3 and D2 is more pronounced:
  • At higher doses 2
  • In individuals with lower baseline 25(OH)D levels 4
  • In younger females compared to older males 4

Pharmacokinetic Differences

• Binding to Vitamin D Binding Protein (DBP):

  • D3 metabolites have stronger binding to DBP in plasma 3
  • This results in longer half-life for D3 metabolites

• Metabolism:

  • D2 has a non-physiologic metabolism compared to D3 3
  • D3 maintains more stable serum levels over time

• Shelf Life:

  • D2 has a shorter shelf life than D3 3

Clinical Applications

Dosing Considerations

• Both forms can be used to treat vitamin D deficiency, but higher doses of D2 may be needed to achieve the same effect as D3 1

• For maintenance therapy after repletion, daily administration of 200-1,000 IU of vitamin D is recommended 1

• In CKD patients, vitamin D supplementation should be guided by serum 25(OH)D levels, with target levels ≥30 ng/mL 1

Special Populations

• In patients with malabsorptive conditions (like after bariatric surgery), intramuscular administration may be more effective than oral supplementation 1

• In CKD patients, the required doses of vitamin D may be higher due to:

  • Reduced sun exposure
  • Limited dietary intake
  • Reduced endogenous synthesis
  • Urinary losses of 25(OH)D and vitamin D-binding protein in nephrotic patients 1

Common Pitfalls and Caveats

• Equivalence Assumption: Despite pharmacopoeias historically regarding D2 and D3 as equivalent and interchangeable, evidence shows they are not equally effective 3

• Inappropriate Substitution: Using D2 when D3 would be more effective, particularly in severe deficiency states

• Monitoring: Failure to monitor 25(OH)D levels after supplementation to confirm adequate repletion

• Confusion with Active Vitamin D: Calcitriol, alfacalcidol, or other active vitamin D analogs should not be used to treat nutritional vitamin D deficiency 1

• Dosing Frequency: While weekly or monthly high-dose vitamin D2 is sometimes used for convenience, daily vitamin D3 may provide more stable serum levels 5