For a female patient with severe vitamin D deficiency, which is better for absorption, cholecalciferol (Vitamin D3) or ergocalciferol (Vitamin D2)?

Cholecalciferol (Vitamin D3) is Superior for Absorption

Cholecalciferol (vitamin D3) is definitively better than ergocalciferol (vitamin D2) for absorption and should be the preferred choice for treating severe vitamin D deficiency in female patients. 1

Evidence for D3 Superiority

Bioefficacy and Potency

• The American College of Cardiology and other guideline societies recommend cholecalciferol over ergocalciferol due to its higher bioefficacy and longer duration of action, with high-quality evidence supporting this recommendation 1
• Cholecalciferol is approximately 3.2-fold more potent than ergocalciferol when comparing physiologic doses, meaning lower doses of D3 are needed to achieve the same serum 25(OH)D levels 2
• When using dosages ≤25 μg/day, serum 25(OH)D increased by only 1.5 nmol/L per 1 μg of cholecalciferol, whereas ergocalciferol required higher doses to achieve similar results 2

Clinical Outcomes

• In a direct comparison study, a 10-day course of 500,000 IU cholecalciferol increased mean serum 25(OH)D by 47 ng/mL, while a single 600,000 IU ergocalciferol dose increased levels by only 10 ng/mL 3
• Ergocalciferol supplementation has been shown to decrease 25(OH)D3 levels by an average of 4 ng/mL in some patients, potentially worsening the deficiency of the more bioactive D3 form 3
• The National Institutes of Health recommends cholecalciferol over ergocalciferol due to its longer duration of action and better bioavailability 1

Recommended Treatment Protocol for Severe Deficiency

Loading Phase

• Administer 50,000 IU of cholecalciferol weekly for 8-12 weeks to rapidly correct severe deficiency 1, 4
• The cholecalciferol loading dose can be calculated using the formula: dose (IU) = 40 × (75 - serum 25(OH)D) × body weight in kg 5

Maintenance Phase

• After normalization, continue with 800-2,000 IU of cholecalciferol daily for long-term maintenance 1
• Target serum 25(OH)D levels should be at least 30 ng/mL for optimal health benefits 1, 6

Critical Monitoring Requirements

• Measure serum 25(OH)D levels after 3-6 months of supplementation using an assay that measures both 25(OH)D2 and 25(OH)D3 1
• Ensure adequate calcium intake of 1,000-1,500 mg daily alongside vitamin D supplementation 1
• Monitor serum calcium and phosphorus levels, particularly in patients with kidney disease or other risk factors for hypercalcemia 6

Common Pitfalls to Avoid

• Do not default to ergocalciferol simply because it is available as a prescription formulation - while 50,000 IU capsules have historically been available only as ergocalciferol in the United States, cholecalciferol is now widely available and should be preferentially prescribed 1
• Avoid assuming that higher doses of ergocalciferol will compensate for its lower bioefficacy - the evidence shows ergocalciferol may actually enhance degradation of the more bioactive 25(OH)D3 metabolite 3
• Do not use ergocalciferol for maintenance therapy - after correcting deficiency with either form, cholecalciferol at 800-1,000 IU daily is recommended for maintenance 4

Special Considerations

• The only clinical scenario where ergocalciferol might be considered is in patients with severe liver failure or intestinal malabsorption syndromes, though even in these cases, cholecalciferol remains the preferred option 7
• In chronic kidney disease patients (stages 3-4), both forms can be used for preventing nutritional deficiency, but cholecalciferol remains superior for treatment 6
• Cholecalciferol has the advantage of allowing flexible dosing schedules (daily, weekly, or monthly) with equivalent efficacy, which can improve adherence 7