Suplmnt

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]

Vitamin D3 (cholecalciferol) Products

Vitamin D2 (ergocalciferol) Products

The Comparison

A Vitamin D3 (cholecalciferol)

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.

B Vitamin D2 (ergocalciferol)

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]

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]

Safety Considerations

  • Upper limit: Adults 19+ years 4,000 IU/day from all sources unless medically supervised. Excess can cause hypercalcemia. [6]
  • Drug interactions: orlistat reduces absorption; corticosteroids impair vitamin D metabolism; thiazide diuretics with vitamin D may raise hypercalcemia risk; high-dose vitamin D may interact with some statins. Discuss with a clinician. [6]
  • Monitoring: If testing, prefer LC-MS/MS methods, especially when supplementing D2 due to assay underestimation of 25(OH)D2. [7]
  • Both forms are generally well tolerated at recommended doses; choose form based on efficacy, preference (e.g., vegan), and testing logistics. [2][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]

Sources

  1. 1.
    Comparison of vitamin D2 and vitamin D3 supplementation in raising serum 25-hydroxyvitamin D status: a systematic review and meta-analysis (2012) [link]
  2. 2.
    Relative Efficacy of Vitamin D2 and Vitamin D3 in Improving Vitamin D Status: Systematic Review and Meta-Analysis (2021) [link]
  3. 3.
    Differential Effects of Oral Boluses of Vitamin D2 vs Vitamin D3 on Vitamin D Metabolism: A Randomized Controlled Trial (2019) [link]
  4. 4.
    Long-term vitamin D3 supplementation is more effective than vitamin D2 in maintaining serum 25(OH)D over winter (2011) [link]
  5. 5.
    Cholecalciferol vs ergocalciferol for 25(OH)D repletion in chronic kidney disease: randomized trial (2017) [link]
  6. 6.
    Vitamin D — Health Professional Fact Sheet (2024) [link]
  7. 7.
    VDSP Intercomparison Study: Immunoassays underestimate 25(OH)D2 (2021) [link]
  8. 8.
    25(OH)D2 half-life is shorter than 25(OH)D3 half-life (2014) [link]
  9. 9.
    Vitamin‑D2 treatment-associated decrease in 25(OH)D3 level is a reciprocal phenomenon: RCT (2019) [link]
  10. 10.
    Baseline assessment of 25(OH)D assay performance (VDSP) (2017) [link]