For a patient with vitamin D deficiency, should I prescribe ergocalciferol or cholecalciferol (Vitamin D3)?

Cholecalciferol (Vitamin D3) is Strongly Preferred Over Ergocalciferol (Vitamin D2)

Prescribe cholecalciferol (vitamin D3) rather than ergocalciferol (vitamin D2) for treating vitamin D deficiency, as D3 has superior bioefficacy, longer duration of action, and maintains serum 25(OH)D levels more effectively. 1

Evidence Supporting Cholecalciferol Superiority

Pharmacologic Advantages of D3

• Cholecalciferol maintains serum 25(OH)D concentrations for significantly longer periods than ergocalciferol, particularly when using intermittent dosing schedules (weekly or monthly). 2, 1
• D3 demonstrates higher bioavailability and bioefficacy compared to D2, making it the preferred formulation according to major guideline societies including the American College of Cardiology. 1
• Research directly comparing the two forms shows that a 10-day course of 500,000 IU cholecalciferol increased mean 25(OH)D levels by 47 ng/mL, while a single 600,000 IU dose of ergocalciferol increased levels by only 10 ng/mL. 3

Potential Harm from Ergocalciferol

• Ergocalciferol supplementation may actually decrease endogenous 25(OH)D3 levels—in one study, a 600,000 IU D2 mega-dose decreased 25(OH)D3 levels by an average of 4 ng/mL in 37 subjects. 3
• This degradation effect on the D3 metabolite represents a significant clinical concern when using ergocalciferol. 3

Practical Treatment Protocol

For Documented Vitamin D Deficiency (<20 ng/mL)

• Prescribe cholecalciferol 50,000 IU weekly for 8-12 weeks as the loading dose regimen. 4, 2, 1
• This produces rapid correction of deficiency with target levels ≥30 ng/mL. 4

Maintenance After Loading Phase

• Transition to cholecalciferol 2,000 IU daily or 50,000 IU monthly once target levels are achieved. 4, 2
• The monthly dosing (50,000 IU) is equivalent to approximately 1,600 IU daily and facilitates adherence. 2

Essential Co-Intervention

• Ensure adequate calcium intake of 1,000-1,500 mg daily from diet plus supplements, as calcium is essential for clinical response to vitamin D therapy. 4, 2

Monitoring Strategy

• Recheck 25(OH)D levels after 3 months of treatment to confirm adequate response, with a target level of ≥30 ng/mL for optimal bone health and fracture prevention. 4, 2
• When using intermittent dosing regimens, measure levels just prior to the next scheduled dose. 2

Why Ergocalciferol Was Historically Used

Historical Context

• In the United States, the prescription high-dose formulation (50,000 IU capsules) was historically available only as ergocalciferol (D2), while D3 was primarily available over-the-counter in lower doses. 1
• This created a prescribing pattern where physicians writing prescriptions for severe deficiency defaulted to the available D2 formulation. 1
• The 2003 National Kidney Foundation K/DOQI guidelines suggested ergocalciferol might be safer than cholecalciferol, though this was based on limited evidence and has been superseded by current guidelines. 1

Current Availability

• Cholecalciferol is now available in prescription-strength 50,000 IU formulations, eliminating the historical barrier to prescribing D3. 5

Critical Pitfall to Avoid

• Do not default to ergocalciferol simply because it appears as the prescription option in your electronic medical record or pharmacy formulary—actively specify cholecalciferol 50,000 IU weekly. 1
• The older practice of prescribing ergocalciferol was driven by availability constraints, not clinical superiority. 1

Special Populations

Malabsorption Syndromes

• For patients with documented malabsorption (post-bariatric surgery, inflammatory bowel disease, celiac disease), consider intramuscular cholecalciferol 50,000 IU, as IM administration results in significantly higher 25(OH)D levels compared to oral supplementation. 2
• When IM is unavailable, use substantially higher oral doses of cholecalciferol: 4,000-5,000 IU daily for 2 months. 2

Chronic Kidney Disease

• For CKD patients with GFR 20-60 mL/min/1.73m², standard nutritional vitamin D replacement with cholecalciferol is appropriate and important. 4, 2
• Do not use active vitamin D analogs (calcitriol, alfacalcidol, doxercalciferol, paricalcitol) to treat nutritional vitamin D deficiency, as they do not correct 25(OH)D levels. 2

Safety Profile

• Daily doses up to 4,000 IU of cholecalciferol are generally safe for adults, with some evidence supporting up to 10,000 IU daily for several months without adverse effects. 2, 5
• The upper safety limit for 25(OH)D is 100 ng/mL. 2
• Toxicity is rare but can occur with prolonged high doses (typically >10,000 IU daily) and may cause hypercalcemia, hypercalciuria, and renal issues. 2