Vitamin D 50,000 IU Divided Dose Regimen
For adults with documented vitamin D deficiency (<20 ng/mL), the standard regimen is 50,000 IU of cholecalciferol (vitamin D3) once weekly for 8-12 weeks, followed by maintenance therapy of 1,500-2,000 IU daily or 50,000 IU monthly. 1, 2
Standard Loading Phase Protocol
Administer 50,000 IU cholecalciferol once weekly for 8 weeks for moderate deficiency (10-20 ng/mL), or extend to 12 weeks for severe deficiency (<10 ng/mL). 1, 2, 3
Cholecalciferol (vitamin D3) is strongly preferred over ergocalciferol (vitamin D2) because it maintains serum 25(OH)D levels longer and has superior bioavailability, particularly with intermittent dosing schedules. 1, 2
Take the 50,000 IU dose with the largest, fattiest meal of the day to maximize absorption, as vitamin D is fat-soluble and requires dietary fat for optimal intestinal uptake. 1
Target Levels and Monitoring
The minimum target 25(OH)D level is ≥30 ng/mL for optimal bone health and anti-fracture efficacy, with anti-fall benefits beginning at ≥24 ng/mL. 1, 2
Recheck 25(OH)D levels 3 months after initiating treatment to allow sufficient time for levels to plateau and accurately reflect response to supplementation, given vitamin D's long half-life. 1, 4, 2
If using intermittent dosing (weekly or monthly), measure levels just prior to the next scheduled dose. 1
Maintenance Phase After Loading
Transition to maintenance therapy with 1,500-2,000 IU daily after completing the 8-12 week loading phase. 1, 2
Alternative maintenance regimen: 50,000 IU monthly (equivalent to approximately 1,600 IU daily) can sustain optimal levels. 1, 2
For elderly patients (≥65 years), a minimum of 800 IU daily is recommended, though higher doses of 700-1,000 IU daily reduce fall and fracture risk more effectively. 1
Essential Co-Interventions
Ensure adequate calcium intake of 1,000-1,500 mg daily from diet plus supplements if needed, as adequate calcium is necessary for clinical response to vitamin D therapy. 1, 2
Calcium supplements should be taken in divided doses of no more than 600 mg at once for optimal absorption, separated by at least 2 hours from the vitamin D dose. 1, 2
Recommend weight-bearing exercise for at least 30 minutes, 3 days per week, to support bone health. 1, 2
Special Populations Requiring Modified Approaches
Malabsorption Syndromes
For patients with malabsorption (inflammatory bowel disease, post-bariatric surgery, celiac disease, pancreatic insufficiency, short-bowel syndrome), intramuscular vitamin D3 50,000 IU is the preferred route when available, as it results in significantly higher 25(OH)D levels and lower rates of persistent deficiency compared to oral supplementation. 1, 5
When IM is unavailable or contraindicated, substantially higher oral doses are required: 50,000 IU 2-3 times weekly for 8-12 weeks, or even daily dosing in severe malabsorption. 1, 6
Post-bariatric surgery patients specifically need at least 2,000 IU daily for maintenance to prevent recurrent deficiency. 1
Chronic Kidney Disease
For CKD patients with GFR 20-60 mL/min/1.73m² (stages 3-4), use standard nutritional vitamin D replacement with cholecalciferol or ergocalciferol, not active vitamin D analogs. 1, 2
CKD patients are at particularly high risk due to reduced sun exposure, dietary restrictions, urinary losses of 25(OH)D, and reduced endogenous synthesis. 1
Monitor serum calcium and phosphorus at least every 3 months during treatment, and discontinue all vitamin D therapy immediately if serum corrected total calcium exceeds 10.2 mg/dL (2.54 mmol/L). 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 vitamin D sequestration in adipose tissue. 4, 6
Without monitoring of 25(OH)D, daily doses of 7,000 IU or intermittent doses of 30,000 IU/week should be considered for prolonged time as prophylactic or maintenance doses in obese patients. 6
Critical Pitfalls to Avoid
Never use active vitamin D analogs (calcitriol, alfacalcidol, doxercalciferol, paricalcitol) to treat nutritional vitamin D deficiency, as they do not correct 25(OH)D levels and bypass normal regulatory mechanisms, carrying higher risk of hypercalcemia. 1, 2
Avoid single very large doses (>300,000 IU) as they may be inefficient or potentially harmful, particularly for fall and fracture prevention. 1, 4, 2
Single annual mega-doses of 500,000-540,000 IU have been associated with adverse outcomes, including increased falls and fractures in clinical trials. 4
Do not supplement patients with normal vitamin D levels, as benefits are only seen in those with documented deficiency. 1, 2
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, 4, 2
The upper safety limit for 25(OH)D is 100 ng/mL, with toxicity typically occurring only with prolonged high doses (>10,000 IU daily) or serum levels >100 ng/mL. 1, 4, 2
Vitamin D toxicity manifests as hypercalcemia, hypercalciuria, suppressed parathyroid hormone, dizziness, and potential renal failure. 1, 4
The 50,000 IU weekly regimen for 8-12 weeks (total cumulative dose of 400,000-600,000 IU) is well-established as safe with no significant adverse events reported in clinical trials. 1
Expected Response
Using the rule of thumb, an intake of 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, 4
The standard 50,000 IU weekly regimen for 8-12 weeks typically raises 25(OH)D levels by approximately 40-70 nmol/L (16-28 ng/mL). 1
If levels remain below 30 ng/mL after 3 months despite compliance, increase the maintenance dose by 1,000-2,000 IU daily (or equivalent intermittent dose). 1