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Vitamin D3 vs Vitamin D2 for efficacy and bioavailability comparison hero image

Vitamin D3 vs Vitamin D2 for efficacy and bioavailability

Evidence Level: robust

For most people seeking the strongest, most durable rise in vitamin D status, choose D3. D2 works, but on average raises and sustains 25(OH)D less, especially with bolus dosing. [1][2]

Across randomized trials and meta-analyses, D3 produces larger and more sustained increases in serum 25(OH)D than D2, particularly with intermittent/high-dose regimens, and has a slightly longer 25(OH)D half-life. D2 remains acceptable (and vegan) but may need higher or more frequent dosing and careful lab methods when monitoring. [1][2][3][4][8][7]

The Comparison

Standardization: Typically as cholecalciferol; potencies 400–10,000 IU/capsule

Dosage: 800–2,000 IU/day for maintenance; higher per clinician for repletion

Benefits

  • More effective at raising/maintaining serum 25(OH)D
  • Longer 25(OH)D half-life
  • Better performance with bolus dosing in RCTs

Drawbacks

  • Animal-derived in most products unless labeled vegan

Safety:Same UL and interactions as D2; see Safety section.

Standardization: As ergocalciferol; Rx 50,000 IU capsules exist

Dosage: 800–2,000 IU/day for maintenance; Rx 50,000 IU weekly used for short courses

Benefits

  • Plant/fungal-derived (vegan)
  • Effective at increasing total 25(OH)D, though typically less than D3

Drawbacks

  • Smaller, less durable rises in 25(OH)D on average
  • More assay variability with 25(OH)D2 measurements

Safety:Same UL and interactions as D3; see Safety section.

Head-to-Head Analysis

Ability to raise 25(OH)D (overall) Critical

Winner:Vitamin D3 (cholecalciferol) Importance: high

Meta-analyses and head-to-head trials show D3 increases total 25(OH)D more than D2 across doses and populations. [1][2]

Bolus/intermittent dosing performance Critical

Winner:Vitamin D3 (cholecalciferol) Importance: high

With large, infrequent doses, D3 outperforms D2 in elevating and maintaining 25(OH)D. [1][3]

Durability/half-life of 25(OH)D Critical

Winner:Vitamin D3 (cholecalciferol) Importance: high

25(OH)D3 has a modestly longer plasma half-life than 25(OH)D2, aiding maintenance. [8]

Daily maintenance efficacy (physiologic doses)

Winner:Vitamin D3 (cholecalciferol) Importance: medium

Long-term daily trials show greater or more sustained 25(OH)D with D3 vs D2. [4]

Effect on endogenous D3 metabolites

Winner:Vitamin D3 (cholecalciferol) Importance: medium

D2 can lower circulating 25(OH)D3 and related metabolites; overall total 25(OH)D still rises but less than with D3. [3]

Assay reliability for monitoring

Winner:Vitamin D3 (cholecalciferol) Importance: medium

Common immunoassays tend to underestimate 25(OH)D2; D3 monitoring is less affected (LC-MS/MS preferred for both). [7]

Special populations (e.g., CKD repletion)

Winner:Vitamin D3 (cholecalciferol) Importance: medium

In CKD, D3 raised 25(OH)D more during therapy than D2 at equal doses. [5]

Dietary preference (vegan suitability)

Winner:Vitamin D2 (ergocalciferol) Importance: low

D2 is plant-derived and widely vegan; note vegan D3 options also exist. [6]

Common Questions

Is D2 ever preferable to D3?

Yes—if you require a vegan option and cannot source vegan D3. D2 still raises total 25(OH)D, though often less than D3. [2]

Does D2 lower my body's D3?

D2 can reduce circulating 25(OH)D3, but total 25(OH)D still increases; a reciprocal effect is seen when taking D3. [3][9]

What dosing strategy is best for quick results?

Intermittent high-dose repletion favors D3 for larger, more sustained 25(OH)D rises. Follow clinician guidance. [1][3]

Do I need a blood test to choose a form?

Not usually; when monitored, ask for LC-MS/MS, especially if using D2 due to assay bias. [7][10]

What's the safe upper limit?

For adults, 4,000 IU/day unless supervised medically; check interactions if on certain meds. [6]

Which Should You Choose?

Rapid repletion or intermittent high-dose protocols

Choose:Vitamin D3 (cholecalciferol)

D3 achieves higher and more sustained 25(OH)D with bolus dosing. [1][3]

Everyday maintenance (800–2,000 IU/day)

Choose:Vitamin D3 (cholecalciferol)

D3 generally yields slightly higher steady-state 25(OH)D over time. [4][2]

Strict vegan preference with limited access to vegan D3

Choose:Vitamin D2 (ergocalciferol)

D2 is reliably vegan and increases 25(OH)D, though may require higher/frequent dosing. [2][6]

Situations where lab monitoring uses immunoassays

Choose:Vitamin D3 (cholecalciferol)

25(OH)D2 is more often underestimated; D3 reduces assay-related misclassification risk. Use LC-MS/MS when possible. [7]

Chronic kidney disease patients needing repletion (non-dialysis)

Choose:Vitamin D3 (cholecalciferol)

Equal-dose RCT favored D3 during active therapy. [5]

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