Treatment of Vitamin D Insufficiency
For vitamin D insufficiency (25(OH)D levels 20-30 ng/mL), prescribe ergocalciferol or cholecalciferol 50,000 IU once weekly for 8-12 weeks, followed by maintenance therapy with 1,500-2,000 IU daily to achieve and maintain levels ≥30 ng/mL. 1, 2
Understanding Vitamin D Insufficiency
Vitamin D insufficiency is defined as serum 25-hydroxyvitamin D levels between 20-30 ng/mL, which places patients at increased risk for secondary hyperparathyroidism, suboptimal bone health, and elevated fracture risk. 1, 3 The treatment goal is to achieve and maintain levels of at least 30 ng/mL, as anti-fracture efficacy begins at this threshold, while anti-fall efficacy starts at 24 ng/mL. 1, 2
Loading Phase Treatment Protocol
Administer 50,000 IU of vitamin D (either D2 or D3) once weekly for 8-12 weeks as the standard loading regimen. 1, 2 This cumulative dose of 400,000-600,000 IU over 8-12 weeks is necessary because standard daily doses would take many months to normalize vitamin D levels. 1
Vitamin D3 vs D2 Selection
Cholecalciferol (vitamin D3) is strongly preferred over ergocalciferol (vitamin D2) because it maintains serum levels longer and has superior bioavailability, particularly when using intermittent dosing schedules. 1, 2 This advantage becomes especially important for weekly or monthly dosing regimens. 1
Maintenance Phase After Loading
After completing the 8-12 week loading phase, transition to maintenance therapy with 1,500-2,000 IU of vitamin D3 daily. 1, 2 An alternative maintenance regimen is 50,000 IU monthly, which provides approximately 1,600 IU daily. 1, 2 Daily dosing is more physiologic, but monthly dosing can achieve similar 25(OH)D concentrations and may improve adherence. 1
For elderly patients (≥65 years), a minimum of 800 IU daily is recommended, though higher doses of 700-1,000 IU daily more effectively reduce fall and fracture risk. 1, 2
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. 1
Weight-bearing exercise for at least 30 minutes, 3 days per week, supports bone health and should be recommended alongside supplementation. 1
Monitoring Protocol
Recheck 25(OH)D levels 3-6 months after initiating treatment to confirm adequate response and guide ongoing therapy. 1, 2 If using intermittent dosing (weekly or monthly), measure levels just prior to the next scheduled dose to assess trough concentrations. 1
The upper safety limit for 25(OH)D is 100 ng/mL and should not be exceeded. 1, 2 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
Special Population Considerations
Chronic Kidney Disease
For patients with CKD stages 3-4 (GFR 20-60 mL/min/1.73m²), standard nutritional vitamin D replacement with ergocalciferol or cholecalciferol is appropriate and recommended. 4, 1, 2 These patients are at particularly high risk for vitamin D deficiency due to reduced sun exposure, dietary restrictions, and increased urinary losses. 1
Malabsorption Syndromes
For patients with documented malabsorption (post-bariatric surgery, inflammatory bowel disease, short-bowel syndrome), intramuscular vitamin D 50,000 IU is preferred when available, as it results in significantly higher 25(OH)D levels and lower rates of persistent deficiency compared to oral supplementation. 1 When IM is unavailable or contraindicated, substantially higher oral doses (4,000-5,000 IU daily) are required. 1
Dark-Skinned or Veiled Individuals
Dark-skinned or veiled individuals with limited sun exposure should receive 800 IU daily without requiring baseline measurement, as they are at high risk for deficiency. 1, 2
Critical Pitfalls to Avoid
Do not use active vitamin D analogs (calcitriol, alfacalcidol, doxercalciferol, paricalcitol) to treat nutritional vitamin D insufficiency, as they do not correct 25(OH)D levels and are reserved for specific conditions like advanced CKD with impaired 1α-hydroxylase activity. 1, 2
Avoid single very large doses exceeding 300,000 IU, as they may be inefficient or potentially harmful, particularly for fall and fracture prevention. 1, 5 The evidence shows that single massive doses (300,000-500,000 IU) should be avoided. 5
Do not supplement patients with normal vitamin D levels (≥30 ng/mL), as benefits are only seen in those with documented insufficiency or deficiency. 1
Safety Profile
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, 6 Toxicity is rare and typically occurs only with prolonged high doses (>10,000 IU daily) or serum levels >100 ng/mL, manifesting as hypercalcemia, hyperphosphatemia, suppressed parathyroid hormone, and hypercalciuria. 1, 2
Expected Response
Using the standard loading regimen of 50,000 IU weekly for 8-12 weeks, most patients will achieve 25(OH)D levels above 30 ng/mL. 1 Patients with the lowest baseline values demonstrate the greatest absolute increase in 25(OH)D levels. 7 After achieving target levels with loading therapy, maintenance dosing of 1,500-2,000 IU daily sustains optimal levels in >90% of the general adult population. 8