What is the recommended vitamin D replacement regimen for patients with confirmed vitamin D deficiency?

Vitamin D Replacement Protocol

Immediate Treatment Recommendation

For confirmed vitamin D deficiency (<20 ng/mL), initiate cholecalciferol (vitamin D3) 50,000 IU once weekly for 8-12 weeks, followed by maintenance therapy of 1,500-2,000 IU daily to achieve and maintain serum 25(OH)D levels ≥30 ng/mL. 1, 2

Treatment Algorithm by Deficiency Severity

Severe Deficiency (<10-12 ng/mL)

• Loading phase: Cholecalciferol 50,000 IU weekly for 12 weeks (not 8 weeks) 1, 2
• This severity significantly increases risk for osteomalacia and rickets, demanding urgent treatment 2
• After loading, transition to 50,000 IU monthly or 2,000 IU daily for maintenance 1, 2

Standard Deficiency (10-20 ng/mL)

• Loading phase: Cholecalciferol 50,000 IU weekly for 8 weeks 1, 2
• Cumulative dose of 400,000 IU over 8 weeks typically increases 25(OH)D by approximately 40-50 ng/mL 3
• Transition to maintenance dosing after completion 2

Insufficiency (20-30 ng/mL)

• If patient has osteoporosis, fracture risk, falls, or is elderly: treat as deficiency 2
• Otherwise: add 1,000 IU daily to current intake and recheck in 3 months 1

Critical: Cholecalciferol (D3) vs Ergocalciferol (D2)

Always prescribe cholecalciferol (D3) over ergocalciferol (D2). 1, 2 D3 maintains serum levels significantly longer and has superior bioavailability, particularly crucial for weekly or monthly dosing schedules 1, 2. While guidelines mention both options, D3 is strongly preferred based on pharmacokinetic superiority 2.

Maintenance Therapy Options

After completing loading phase, choose one:

• Daily dosing: 1,500-2,000 IU daily (preferred for most patients) 1, 2
• Monthly dosing: 50,000 IU once monthly (equivalent to ~1,600 IU daily) 1, 2
• For elderly ≥65 years: Minimum 800 IU daily, though 700-1,000 IU daily more effectively reduces falls and fractures 1, 2

Essential Co-Interventions

Calcium supplementation is mandatory for clinical response: 2

• Total daily calcium: 1,000-1,500 mg from diet plus supplements 1, 2
• Divide calcium supplements into doses ≤600 mg for optimal absorption 1, 2
• Take vitamin D with food to enhance absorption 4

Target Levels and Monitoring

Target serum 25(OH)D ≥30 ng/mL for anti-fracture efficacy 1, 2:

• Anti-fall efficacy begins at ≥24 ng/mL 1, 2
• Upper safety limit is 100 ng/mL 1, 2
• Recheck 25(OH)D after 3-6 months of treatment 1, 2
• If using intermittent dosing (weekly/monthly), measure just before next scheduled dose 1

Special Populations Requiring Modified Approach

Malabsorption Syndromes

For post-bariatric surgery, inflammatory bowel disease, or short-bowel syndrome: 1

• First-line: Intramuscular cholecalciferol 50,000 IU results in significantly higher levels than oral 1
• If IM unavailable: Increase oral dosing to 4,000-5,000 IU daily for 2 months, then minimum 2,000 IU daily maintenance 1
• IM availability varies by country and may be contraindicated with anticoagulation 1

Chronic Kidney Disease (CKD Stages 3-4)

• Use standard nutritional vitamin D (cholecalciferol or ergocalciferol), same dosing as general population 1, 2
• Never use active vitamin D analogs (calcitriol, alfacalcidol, doxercalciferol, paricalcitol) for nutritional deficiency 1, 2
• These analogs do not correct 25(OH)D levels and are reserved for advanced CKD with impaired 1α-hydroxylase activity 2

High-Risk Groups Not Requiring Baseline Testing

Treat empirically with 800 IU daily: 1, 2

• Elderly ≥65 years
• Dark-skinned or veiled individuals with limited sun exposure
• Institutionalized individuals

Critical Pitfalls to Avoid

Do not use single ultra-high doses (>300,000 IU) - these are inefficient or potentially harmful, particularly for fall and fracture prevention 1, 2

Do not supplement patients with normal vitamin D levels - benefits only occur in documented deficiency 1, 2

Correct vitamin D deficiency before initiating bisphosphonates to prevent severe hypocalcemia 2

Do not confuse nutritional vitamin D with active vitamin D analogs - they serve completely different purposes 2

Safety Profile

• Daily doses up to 4,000 IU are safe for adults 1, 2
• Some evidence supports up to 10,000 IU daily for several months without adverse effects 1
• Toxicity is rare, typically requiring prolonged intake >10,000 IU daily 1, 2
• Toxicity manifests as hypercalcemia, hypercalciuria, and potential renal complications 1
• Monitor calcium levels, especially in CKD patients 2

Practical Dosing Calculation

Rule of thumb: 1,000 IU daily increases serum 25(OH)D by approximately 10 ng/mL, though individual response varies due to genetic polymorphisms in vitamin D metabolism 1, 3

For precise loading dose calculation: Dose (IU) = 40 × (75 - current serum 25(OH)D) × body weight in kg 3

This accounts for body weight, baseline level, and target of 75 nmol/L (30 ng/mL) 3

Expected Response

After 50,000 IU weekly for 12 weeks (total 600,000 IU), expect serum 25(OH)D increase of approximately 60-70 ng/mL from baseline 1, 3. Most severely deficient patients (<30 nmol/L) will achieve target levels with this regimen 3.