What is the preferred form of vitamin D supplementation, vitamin D2 or vitamin D3, for patients with a history of vitamin D deficiency or those at risk of osteoporosis?

Vitamin D3 is Preferred Over Vitamin D2

Vitamin D3 (cholecalciferol) should be used preferentially over vitamin D2 (ergocalciferol) for supplementation in patients with vitamin D deficiency or at risk of osteoporosis, as D3 is more effective at maintaining serum 25(OH)D levels, particularly when using intermittent dosing regimens. 1

Key Differences Between D2 and D3

While both forms can be used for supplementation, important distinctions exist:

• Vitamin D3 is more potent for maintenance therapy: D3 demonstrates superior efficacy compared to D2 when using longer dosing intervals (weekly or monthly administration) 1

• Source differences: D3 (cholecalciferol) is the animal-derived form found primarily in oily fish, while D2 (ergocalciferol) is the plant/mushroom form that is almost absent in the diet 2

• Availability varies by country: The accessibility of D2 versus D3 differs significantly between countries, which may influence practical prescribing decisions 2

Recommended Dosing Strategy

For Vitamin D Deficiency (<20 ng/mL):

Loading Phase:

• Administer 50,000 IU of either D2 or D3 once weekly for 8-12 weeks 1
• For severe deficiency (<10 ng/mL), extend to 12 weeks followed by monthly maintenance 1

Maintenance Phase:

• Use 800-1000 IU daily of vitamin D (preferably D3) 1
• This daily dosing approach is superior to intermittent high-dose regimens for fall and fracture prevention 3

For At-Risk Populations Without Testing:

• Dark-skinned, veiled, elderly, or institutionalized individuals: 800 IU daily without baseline testing 2, 1

Clinical Outcomes Supporting D3 Preference

Fracture and Fall Prevention:

• Daily vitamin D3 supplementation (800 IU) combined with calcium (1000 mg) reduces falls and non-vertebral fractures in elderly patients with vitamin D deficiency 3
• A single loading dose of D3 (versus placebo) reduced falls rate by 57% in hip fracture patients (250 vs 821.4 falls per 1000 patient-days) 2

Target Serum Levels:

• Aim for 25(OH)D levels of 30-60 ng/mL (or 75 nmol/L minimum) for optimal bone health and fracture prevention 1, 4
• Levels above 30 ng/mL are recommended for patients with musculoskeletal health problems, cardiovascular disease, autoimmune disease, and cancer 2

Important Caveats

Avoid High Intermittent Dosing:

• Intermittent high-dose supplementation (≥60,000 IU monthly or higher) may paradoxically increase falls, fractures, and mortality risk in certain populations 3
• If intermittent dosing is necessary due to availability or reimbursement issues, use the smallest available dose (≤50,000 IU) with the shortest interval between doses 3

Monitoring Requirements:

• Measure serum 25(OH)D levels 3-6 months after initiating treatment to ensure adequate dosing 1
• Check serum calcium (adjusted for albumin) 1 month after completing loading regimen to unmask potential primary hyperparathyroidism 5
• Use assays measuring both 25(OH)D2 and 25(OH)D3 2

Safety Considerations:

• Daily doses up to 4000 IU are generally safe for adults 1
• Upper safety limit for 25(OH)D is 100 ng/mL 2, 1
• Avoid single very large doses (>300,000 IU) as they may be inefficient or harmful 1

Special Clinical Scenarios

Malabsorption:

• Patients not responding to oral supplementation may require parenteral vitamin D (typically 50,000 IU IM) 1

Concurrent Antiresorptive Therapy:

• When prescribing bisphosphonates or other osteoporosis medications, ensure vitamin D sufficiency first, as adequate levels are necessary for optimal therapeutic response 2

Drug Interactions:

• Mineral oil interferes with fat-soluble vitamin absorption including vitamin D 6
• Thiazide diuretics in hypoparathyroid patients receiving vitamin D may cause hypercalcemia 6