What dose of vitamin D3 (in mg) should an adult with serum 25‑hydroxy‑vitamin D <20 ng/mL take for repletion and subsequent maintenance?

Vitamin D3 Dosing for Deficiency (<20 ng/mL)

For adults with documented vitamin D deficiency (serum 25-hydroxyvitamin D <20 ng/mL), initiate 50,000 IU of cholecalciferol (vitamin D3) once weekly for 8–12 weeks, followed by maintenance therapy of 2,000 IU daily to achieve and sustain target levels ≥30 ng/mL. 1

Understanding the Conversion: IU to mg

• Vitamin D dosing is standardized in International Units (IU), not milligrams, because biological activity varies by formulation 1
• The conversion is: 1 mcg (microgram) = 40 IU 1
• Therefore, 50,000 IU = 1,250 mcg = 1.25 mg 1
• Daily maintenance of 2,000 IU = 50 mcg = 0.05 mg 1

Initial Loading Phase Protocol

• Standard regimen: 50,000 IU (1.25 mg) of vitamin D3 once weekly for 8–12 weeks 1
• Use 12 weeks for severe deficiency (<10 ng/mL) and 8 weeks for moderate deficiency (10–20 ng/mL) 1
• Cholecalciferol (D3) is strongly preferred over ergocalciferol (D2) because it maintains serum levels longer and has superior bioavailability, particularly with intermittent dosing 1
• This cumulative dose of 400,000–600,000 IU over 8–12 weeks typically raises 25(OH)D levels by 40–70 nmol/L (16–28 ng/mL) 1

Maintenance Phase After Loading

• Transition to 2,000 IU daily after completing the loading regimen to sustain levels ≥30 ng/mL 1
• Alternative maintenance: 50,000 IU monthly (equivalent to approximately 1,600 IU daily) 1
• For elderly patients ≥65 years, minimum maintenance is 800 IU daily, though 700–1,000 IU daily more effectively reduces fall and fracture risk 1

Target Serum Levels and Clinical Endpoints

• Minimum target: 30 ng/mL for anti-fracture efficacy 1
• Anti-fall efficacy begins at 24 ng/mL, but fracture prevention requires ≥30 ng/mL 1
• Optimal range: 30–80 ng/mL for musculoskeletal health, cardiovascular protection, and other benefits 1, 2
• Upper safety limit: 100 ng/mL—toxicity risk increases above this threshold 1, 2

Monitoring Protocol

• Recheck 25(OH)D levels 3 months after initiating treatment to assess response and guide ongoing therapy 1
• If using intermittent dosing (weekly or monthly), measure levels just prior to the next scheduled dose 1
• Once stable and at target, recheck annually 1
• Monitor serum calcium every 3 months during treatment to detect hypercalcemia early 1

Essential Co-Interventions

• Ensure adequate calcium intake of 1,000–1,500 mg daily from diet plus supplements if needed 1
• Calcium supplements should be taken 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

Special Populations Requiring Modified Dosing

Malabsorption Syndromes

• For post-bariatric surgery, inflammatory bowel disease, celiac disease, or pancreatic insufficiency, intramuscular vitamin D3 50,000 IU is the preferred route 1
• When IM is unavailable, use substantially higher oral doses: 4,000–5,000 IU daily for 2 months, then at least 2,000 IU daily for maintenance 1, 3
• IM administration results in significantly higher 25(OH)D levels and lower rates of persistent deficiency compared to oral supplementation in malabsorptive conditions 1

Obesity

• Obese patients may require higher doses (6,000–10,000 IU daily as treatment, followed by maintenance doses of 3,000–6,000 IU daily) due to sequestration of vitamin D in adipose tissue 2, 3
• Without monitoring, 7,000 IU daily or 30,000 IU weekly should be considered for prolonged maintenance in obese patients 3

Chronic Kidney Disease (CKD Stages 3–4)

• Use standard nutritional vitamin D (cholecalciferol or ergocalciferol), not active vitamin D analogs 1
• CKD patients are at particularly high risk due to reduced sun exposure, dietary restrictions, and urinary losses 1
• Never use calcitriol, alfacalcidol, doxercalciferol, or paricalcitol to treat nutritional vitamin D deficiency—these are reserved for advanced CKD with impaired 1α-hydroxylase activity 1

Critical Pitfalls to Avoid

• Avoid single ultra-high loading doses (>300,000–540,000 IU) as they have been associated with increased falls and fractures 1, 2
• Do not use active vitamin D analogs (calcitriol, alfacalcidol) to treat nutritional deficiency—they bypass normal regulatory mechanisms and dramatically increase hypercalcemia risk 1
• Do not rely on standard daily allowances (600–800 IU) to correct deficiency—these doses are insufficient and would take many weeks to normalize low levels 1
• Discontinue all vitamin D immediately if serum corrected total calcium exceeds 10.2 mg/dL (2.54 mmol/L) 1

Alternative High-Dose Regimens for Severe Deficiency

• For severe deficiency with symptoms or high fracture risk, consider 8,000 IU daily for 4 weeks, then 4,000 IU daily for 2 months 1
• For recalcitrant cases or severe malabsorption, escalate to 50,000 IU cholecalciferol 2–3 times weekly for 8–12 weeks 1
• For critically ill patients with levels <12.5 ng/mL, a single dose of 500,000 IU vitamin D3 within a week after admission can be administered 1

Safety Considerations

• Daily doses up to 4,000 IU are completely safe for adults, with some evidence supporting up to 10,000 IU daily for several months without adverse effects 1, 2, 4
• Toxicity typically occurs only with prolonged daily doses >10,000 IU or serum levels >100 ng/mL 1, 2
• Symptoms of toxicity include hypercalcemia, hyperphosphatemia, suppressed PTH, and hypercalciuria 1

Expected Response and Rule of Thumb

• As a general rule, 1,000 IU vitamin D daily increases serum 25(OH)D by approximately 10 ng/mL, though individual responses vary due to genetic differences in vitamin D metabolism 1, 2
• The standard 50,000 IU weekly regimen for 8–12 weeks should bring most patients from deficiency (<20 ng/mL) to at least 28–40 ng/mL if responding normally 1, 5