What is the recommended vitamin D3 supplementation regimen for an adult with vitamin D deficiency (serum 25‑hydroxyvitamin D <20 ng/mL)?

Vitamin D Deficiency Supplementation Regimen

For adults with documented vitamin D deficiency (serum 25-hydroxyvitamin D <20 ng/mL), the standard evidence-based regimen is oral cholecalciferol (vitamin D3) 50,000 IU once weekly for 8–12 weeks, followed by maintenance therapy of 800–2,000 IU daily to achieve and sustain a target serum level ≥30 ng/mL. 1

Loading Phase Protocol

Standard Dosing

• Administer 50,000 IU of vitamin D3 (cholecalciferol) once weekly for 8 weeks if the baseline level is 10–20 ng/mL (moderate deficiency) 1, 2
• Extend the loading phase to 12 weeks if the baseline level is <10 ng/mL (severe deficiency) 1, 3
• Vitamin D3 is strongly preferred over vitamin D2 (ergocalciferol) because it maintains serum concentrations longer and demonstrates superior bioavailability, particularly with intermittent dosing schedules 1, 3

Alternative Daily Loading Regimen

• For patients who prefer daily dosing or have difficulty with weekly schedules, prescribe 4,000–5,000 IU daily for 8–12 weeks 1, 4
• This cumulative approach delivers approximately 600,000 IU over the loading period, which is necessary to replenish depleted vitamin D stores 1, 5

Maintenance Phase

Standard Maintenance Dosing

• After completing the loading phase, transition to 800–2,000 IU of vitamin D3 daily 1, 3, 2
• The specific maintenance dose within this range depends on individual risk factors: use 800 IU for low-risk patients, 1,000–1,500 IU for moderate-risk patients, and 2,000 IU for high-risk patients 1, 6
• An alternative intermittent maintenance regimen is 50,000 IU once monthly (equivalent to approximately 1,600 IU daily) 1

Higher Maintenance Doses for At-Risk Populations

• Obesity (BMI ≥30 kg/m²): 2,000–4,000 IU daily, as adipose tissue sequesters vitamin D and reduces bioavailability 1, 6, 4
• Dark skin pigmentation: 800–2,000 IU daily without baseline testing, as melanin reduces cutaneous vitamin D synthesis by 2–9 fold 1, 6
• Elderly patients (≥65 years): minimum 800 IU daily, with 1,000 IU daily preferred to reduce fall and fracture risk by approximately 19–20% 1, 6
• Chronic kidney disease (stages 3–4, GFR 20–60 mL/min/1.73m²): use standard nutritional vitamin D (cholecalciferol or ergocalciferol) at 800–2,000 IU daily; never use active vitamin D analogs (calcitriol, alfacalcidol, doxercalciferol, paricalcitol) for nutritional deficiency 1
• Malabsorption syndromes (post-bariatric surgery, inflammatory bowel disease, celiac disease, pancreatic insufficiency): 2,000–6,000 IU daily orally, or consider intramuscular vitamin D3 50,000 IU if oral supplementation fails 1, 6, 7

Target Serum Levels and Clinical Endpoints

• Target serum 25-hydroxyvitamin D: ≥30 ng/mL for optimal musculoskeletal health, fracture prevention, and fall reduction 1, 3, 8, 2
• Anti-fracture efficacy begins at 30 ng/mL and continues to improve up to 44 ng/mL 1
• Anti-fall efficacy begins at 24 ng/mL 1
• Upper safety limit: 100 ng/mL; levels above this threshold increase toxicity risk 1, 6

Monitoring Protocol

Initial Follow-Up

• Recheck serum 25-hydroxyvitamin D 3 months after initiating or adjusting supplementation to allow levels to plateau, given vitamin D's long half-life 1, 6, 3, 8
• If using intermittent dosing (weekly or monthly), measure the level just prior to the next scheduled dose 1

Ongoing Monitoring

• Once the target level (≥30 ng/mL) is achieved and stable, recheck annually 1
• Check serum calcium (corrected for albumin) 1 month after completing the loading regimen to unmask primary hyperparathyroidism 8
• For patients on high-dose therapy (>4,000 IU daily), monitor serum calcium and phosphorus every 3 months 1

Essential Co-Interventions

• Ensure adequate calcium intake of 1,000–1,500 mg daily from diet plus supplements, as vitamin D enhances calcium absorption and adequate calcium is necessary for bone health 1, 3, 2
• Calcium supplements should be taken in divided doses of ≤600 mg for optimal absorption 1
• Recommend weight-bearing exercise ≥30 minutes, 3 days per week to support bone health 1

Safety Thresholds and Discontinuation Criteria

• Daily doses up to 4,000 IU are completely safe for long-term use in adults 1, 6, 5
• Limited evidence supports doses up to 10,000 IU daily for several months without adverse effects 1, 6
• Immediately discontinue all vitamin D supplementation if serum calcium rises above 10.2 mg/dL (2.54 mmol/L) 1
• Vitamin D toxicity typically occurs only with daily intake >100,000 IU or serum 25-hydroxyvitamin D >100 ng/mL, manifesting as hypercalcemia, hyperphosphatemia, suppressed parathyroid hormone, and hypercalciuria 1, 5

Critical Pitfalls to Avoid

• Do not use single annual mega-doses (≥300,000–500,000 IU), as they are inefficient and paradoxically increase fall and fracture risk 1, 6, 5
• Do not 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
• Do not rely on sun exposure for vitamin D repletion due to increased skin cancer risk from UVB radiation 1
• Do not measure 25-hydroxyvitamin D earlier than 3 months after starting or changing supplementation, as premature testing yields inaccurate results 1, 6
• Do not assume all patients respond identically; individual response varies due to genetic polymorphisms in vitamin D metabolism, body composition (obesity, muscle mass), and concurrent medications 1, 4
• Do not forget to verify patient adherence before increasing doses for inadequate response, as poor compliance is a common reason for treatment failure 1

Special Populations Requiring Modified Approaches

Malabsorption Syndromes

• For documented malabsorption (post-bariatric surgery, inflammatory bowel disease, short bowel syndrome, untreated celiac disease), intramuscular vitamin D3 50,000 IU is the preferred route, as it achieves significantly higher serum levels and lower rates of persistent deficiency compared with oral supplementation 1
• When IM is unavailable or contraindicated, use substantially higher oral doses: 4,000–5,000 IU daily for 2 months, then at least 2,000 IU daily for maintenance 1, 6, 7

Chronic Kidney Disease

• For CKD stages 3–4 (GFR 20–60 mL/min/1.73m²), use standard nutritional vitamin D replacement (cholecalciferol or ergocalciferol) with the same loading and maintenance regimens as the general population 1
• CKD patients are at particularly high risk due to reduced sun exposure, dietary restrictions, and urinary losses of 25-hydroxyvitamin D 1
• Reserve active vitamin D sterols only for advanced CKD with PTH >300 pg/mL despite vitamin D repletion 1

Pregnancy

• Pregnant individuals require an additional 600 IU daily beyond baseline needs, for a total of approximately 1,000–1,200 IU daily 6
• Check vitamin D status before conception or early in pregnancy 1