What vitamin D repletion regimen should be initiated for an adult with confirmed deficiency and no contraindications such as hypercalcemia, active granulomatous disease, or severe renal impairment?

Vitamin D Repletion Regimen for Adult Deficiency

Standard Loading Phase for Confirmed Deficiency

For adults with confirmed vitamin D deficiency (<20 ng/mL), initiate ergocalciferol (vitamin D₂) or cholecalciferol (vitamin D₃) 50,000 IU once weekly for 8–12 weeks, with cholecalciferol preferred due to superior bioavailability and longer maintenance of serum levels. 1, 2

• Use 12 weeks for severe deficiency (<10 ng/mL) and 8 weeks for moderate deficiency (10–20 ng/mL) 1
• Cholecalciferol (D₃) maintains serum 25(OH)D concentrations longer than ergocalciferol (D₂), particularly with intermittent dosing schedules 1, 2
• Both formulations are acceptable, but D₃ is strongly preferred when using weekly or monthly regimens 1

Maintenance Therapy After Loading

After completing the loading phase, transition to maintenance therapy with 800–2,000 IU daily or 50,000 IU monthly (equivalent to approximately 1,600 IU daily) to sustain levels ≥30 ng/mL. 1

• The monthly 50,000 IU regimen improves adherence while maintaining adequate levels 1
• For elderly patients (≥65 years), use a minimum of 800 IU daily, though 700–1,000 IU daily more effectively reduces fall and fracture risk 1
• Target serum 25(OH)D level is ≥30 ng/mL for optimal anti-fracture efficacy 1

Essential Co-Interventions

Ensure adequate calcium intake of 1,000–1,500 mg daily from diet plus supplements if needed, as calcium is necessary for clinical response to vitamin D therapy. 1, 2

• Take calcium supplements in divided doses of no more than 600 mg at once for optimal absorption 1
• Administer vitamin D with the largest, fattiest meal of the day to maximize absorption 1

Monitoring Protocol

Recheck serum 25(OH)D levels 3 months after completing the loading phase to allow levels to plateau and accurately reflect treatment response. 1

• If levels remain <30 ng/mL, increase the maintenance dose by 1,000–2,000 IU daily (or equivalent intermittent dose) 1
• Once target levels are achieved and stable, annual monitoring is sufficient 1
• Verify patient adherence before increasing doses for inadequate response 1

Expected Clinical Response

Using the general rule, each 1,000 IU of daily vitamin D intake increases serum 25(OH)D by approximately 10 ng/mL, though individual responses vary. 1

• The standard 50,000 IU weekly regimen for 12 weeks typically raises 25(OH)D levels by 40–70 nmol/L (16–28 ng/mL) 1
• Anti-fall efficacy begins at achieved 25(OH)D levels of at least 24 ng/mL, while anti-fracture efficacy requires ≥30 ng/mL 1

Critical Safety Considerations

Daily doses up to 4,000 IU are generally safe for adults; toxicity typically occurs only with prolonged daily doses exceeding 10,000 IU or serum levels >100 ng/mL. 1

• The upper safety limit for serum 25(OH)D is 100 ng/mL 1
• Avoid single very large doses (>300,000 IU) as they may be inefficient or potentially harmful 1
• Never use active vitamin D analogs (calcitriol, alfacalcidol, doxercalciferol, paricalcitol) to treat nutritional vitamin D deficiency, as they bypass normal regulatory mechanisms and dramatically increase hypercalcemia risk. 1, 3

Special Population: Malabsorption Syndromes

For patients with documented malabsorption (post-bariatric surgery, inflammatory bowel disease, celiac disease, pancreatic insufficiency), intramuscular vitamin D₃ 50,000 IU is the preferred route when available. 1

• IM administration results in significantly higher 25(OH)D levels and lower rates of persistent deficiency compared to oral supplementation in malabsorptive conditions 1
• When IM is unavailable, use substantially higher oral doses: 4,000–5,000 IU daily for 2 months 1
• Post-bariatric surgery patients require at least 2,000 IU daily maintenance to prevent recurrent deficiency 1

Special Population: Chronic Kidney Disease

For CKD stages 3–4 (GFR 20–60 mL/min/1.73 m²), use standard nutritional vitamin D replacement with ergocalciferol or cholecalciferol, not active vitamin D analogs. 3

• CKD patients are at particularly high risk due to reduced sun exposure, dietary restrictions, and urinary losses 3
• Monitor serum calcium and phosphorus monthly for the first 3 months, then every 3 months thereafter 3
• Discontinue all vitamin D therapy immediately if serum corrected total calcium exceeds 10.2 mg/dL (2.54 mmol/L) 3

Common Pitfalls to Avoid

• Do not rely on sun exposure for vitamin D repletion due to increased skin cancer risk 1
• Do not use active vitamin D sterols for nutritional deficiency; reserve these only for advanced CKD with PTH >300 pg/mL despite vitamin D repletion 3
• Do not measure 25(OH)D levels too early (<3 months); vitamin D has a long half-life and levels need adequate time to stabilize 1
• Do not ignore compliance issues; poor adherence is a common reason for inadequate response 1