How should I treat an adult with vitamin D deficiency (serum 25‑hydroxy‑vitamin D <20 ng/mL), including loading and maintenance dosing and adjustments for elderly, malabsorption, chronic kidney disease, pregnancy, or hyperparathyroidism?

Treatment of Vitamin D Deficiency in Adults

Initial Loading Phase

For adults with documented vitamin D deficiency (serum 25-hydroxyvitamin D <20 ng/mL), administer ergocalciferol or cholecalciferol 50,000 IU once weekly for 8–12 weeks. 1, 2

• Use 8 weeks for moderate deficiency (10–20 ng/mL) and 12 weeks for severe deficiency (<10 ng/mL). 1
• Cholecalciferol (vitamin D3) is preferred over ergocalciferol (vitamin D2) because it maintains serum levels longer and has superior bioavailability, particularly with intermittent dosing schedules. 1
• This loading regimen typically raises serum 25-hydroxyvitamin D by approximately 40–70 nmol/L (16–28 ng/mL), bringing most patients to at least 30 ng/mL. 1

Alternative high-dose daily regimen: For patients who prefer daily dosing or have difficulty with weekly schedules, prescribe 4,000–5,000 IU cholecalciferol daily for 2–3 months. 2, 3

• This approach is particularly useful in obese patients, those with liver disease, or malabsorption syndromes who may require sustained higher doses. 3
• A rule of thumb: 1,000 IU daily raises serum 25-hydroxyvitamin D by approximately 10 ng/mL. 1

Maintenance Phase

After achieving target levels (≥30 ng/mL), transition to maintenance therapy with 800–2,000 IU cholecalciferol daily or 50,000 IU monthly (equivalent to approximately 1,600 IU daily). 1, 2

• For elderly patients (≥65 years), a minimum of 800 IU daily is recommended even without baseline measurement, though higher doses of 700–1,000 IU daily more effectively reduce fall and fracture risk. 1
• For younger adults (19–70 years), 600–800 IU daily is typically sufficient for maintenance. 1
• Target serum level is ≥30 ng/mL for optimal anti-fracture efficacy; levels ≥24 ng/mL provide anti-fall benefits. 1

Essential Co-Interventions

Ensure adequate calcium intake of 1,000–1,500 mg daily from diet plus supplements. 1, 2

• Calcium is essential for clinical response to vitamin D therapy; vitamin D alone is less effective for bone health. 1, 2
• Calcium supplements should be taken in divided doses of no more than 600 mg at once for optimal absorption. 1
• Separate calcium supplements from iron-containing medications by at least 2 hours to prevent absorption interference. 1

Administer vitamin D with the largest, fattiest meal of the day to maximize absorption, as it is a fat-soluble vitamin requiring dietary fat for optimal intestinal uptake. 1

Monitoring Protocol

Recheck serum 25-hydroxyvitamin D levels 3 months after initiating treatment to allow levels to plateau and accurately reflect treatment response. 1, 2

• If using intermittent dosing (weekly or monthly), measure levels just prior to the next scheduled dose. 1
• Once target levels are achieved and stable, recheck annually. 1
• Individual response to supplementation is variable due to genetic differences in vitamin D metabolism, making monitoring essential. 1

Monitor serum calcium and phosphorus at least every 3 months during high-dose therapy to detect hypercalcemia early. 1

• Discontinue all vitamin D supplementation immediately if serum corrected total calcium exceeds 10.2 mg/dL (2.54 mmol/L). 1
• If serum phosphorus exceeds 4.6 mg/dL (1.49 mmol/L), add or increase phosphate binder dose; if hyperphosphatemia persists, discontinue vitamin D. 1

Special Populations

Elderly Patients (≥65 Years)

Prescribe a minimum of 800 IU cholecalciferol daily, even without baseline measurement. 1

• Higher doses of 700–1,000 IU daily reduce fall risk by approximately 19% and fracture risk by 18–20% when serum levels reach ≥30 ng/mL. 1
• Doses <400 IU daily are ineffective for achieving target concentrations and should be avoided. 1
• A standard multivitamin providing ~400 IU is insufficient for this population. 1

Malabsorption Syndromes

For patients with documented malabsorption (post-bariatric surgery, inflammatory bowel disease, celiac disease, pancreatic insufficiency, short-bowel syndrome), intramuscular vitamin D3 50,000 IU is the preferred route. 1, 2

• IM administration results in significantly higher 25-hydroxyvitamin D levels and lower rates of persistent deficiency compared to oral supplementation. 1
• When IM is unavailable or contraindicated (anticoagulation, infection risk), use substantially higher oral doses: 4,000–5,000 IU cholecalciferol daily for 2 months. 1, 3
• Post-bariatric surgery patients specifically require at least 2,000 IU daily to prevent recurrent deficiency. 1
• For severe malabsorption following bariatric surgery, doses may escalate to 50,000 IU 1–3 times weekly. 1

Chronic Kidney Disease (CKD)

For CKD stages 3–4 (GFR 20–60 mL/min/1.73 m²), use standard nutritional vitamin D replacement with cholecalciferol or ergocalciferol. 1, 2

• CKD patients are at particularly high risk due to reduced sun exposure, dietary restrictions, urinary losses of 25-hydroxyvitamin D, and reduced endogenous synthesis. 1
• Use the same loading regimen (50,000 IU weekly for 8–12 weeks) but potentially higher maintenance doses. 1
• Never use active vitamin D analogs (calcitriol, alfacalcidol, doxercalciferol, paricalcitol) to treat nutritional vitamin D deficiency, as they bypass normal regulatory mechanisms and carry higher risk of hypercalcemia. 1, 2
• Active vitamin D sterols should only be used for advanced CKD with PTH >300 pg/mL despite vitamin D repletion. 1

Pregnancy

Pregnant women with vitamin D deficiency require treatment, as pregnancy increases vitamin D demands. 1

• Use the standard loading regimen of 50,000 IU weekly for 8–12 weeks, followed by maintenance dosing of 1,000–2,000 IU daily. 1
• Ensure adequate calcium intake of 1,000–1,500 mg daily. 1

Hyperparathyroidism

Levels below 15 ng/mL are associated with greater severity of secondary hyperparathyroidism, even in dialysis patients. 1

• Treat vitamin D deficiency with standard loading doses to suppress secondary hyperparathyroidism. 1
• Restoring serum 25-hydroxyvitamin D to ≥30 ng/mL suppresses secondary hyperparathyroidism, reduces bone-turnover activity, and improves bone mineral density. 1
• Monitor PTH levels alongside vitamin D and calcium during treatment. 1

Safety Considerations

Daily doses up to 4,000 IU are generally safe for adults, with some evidence supporting up to 10,000 IU daily for several months without adverse effects. 1, 2, 3, 4

• The upper safety limit for serum 25-hydroxyvitamin D is 100 ng/mL; concentrations above this increase toxicity risk. 1
• Vitamin D toxicity is rare and typically occurs only with prolonged daily doses exceeding 10,000 IU or serum levels above 100 ng/mL. 1
• Toxicity symptoms include hypercalcemia, hyperphosphatemia, suppressed parathyroid hormone, and hypercalciuria. 1

Avoid single very large doses (>300,000 IU), as they may be inefficient or potentially harmful, particularly for fall and fracture prevention. 1

Critical Pitfalls to Avoid

Never use active vitamin D analogs (calcitriol, alfacalcidol, doxercalciferol, paricalcitol) to treat nutritional vitamin D deficiency. 1, 2

• These agents bypass normal regulatory mechanisms, do not correct 25-hydroxyvitamin D levels, and dramatically increase hypercalcemia risk. 1
• They are reserved for advanced CKD with impaired 1α-hydroxylase activity. 1

Do not rely on sun exposure for vitamin D deficiency prevention due to increased skin cancer risk from UVB radiation. 1

Verify patient adherence before increasing doses for inadequate response; poor compliance is a common reason for treatment failure. 1

Ensure total 25-hydroxyvitamin D (D2 and D3) is measured if the patient is on ergocalciferol (vitamin D2) supplements. 1

Do not restart vitamin D supplementation after toxicity until serum calcium has been normal for at least 4 weeks and 25-hydroxyvitamin D levels fall below 100 ng/mL. 1