What is the best method to assess vitamin D (25-hydroxyvitamin D) levels in patients?

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Last updated: January 12, 2026View editorial policy

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Best Method to Check Vitamin D Levels

Order a serum 25-hydroxyvitamin D [25(OH)D] test that measures both the D2 and D3 forms combined, using a laboratory certified by the CDC's Vitamin D Standardization Program, and request results in ng/mL. 1

The Standard Test

  • Serum 25-hydroxyvitamin D is the single best and most reliable biochemical marker for assessing total body vitamin D status 2, 1, 3
  • The test must measure both 25(OH)D2 (ergocalciferol) and 25(OH)D3 (cholecalciferol) forms, as both contribute to your patient's total vitamin D stores 2, 1
  • If the laboratory reports D2 and D3 separately, ensure they provide the sum as the primary result 1

Sample Collection Specifics

  • Use serum as your sample of choice 2, 1
  • Avoid gel separator tubes when possible, particularly if the lab uses LC-MS/MS methodology, as gel tubes can interfere with measurement accuracy 1
  • The timing of blood draw is not critical since 25(OH)D is very stable in serum 1

Laboratory Quality Matters Significantly

  • Verify that your laboratory participates in the CDC's Vitamin D Standardization Certification Program or DEQAS (Vitamin D External Quality Assurance Scheme) 1
  • This verification step is critical because inter-laboratory variability can cause 4-32% variation in whether a patient is classified as deficient or not, depending on which assay is used 2, 1
  • Despite ongoing standardization efforts, significant differences persist among various methods and laboratories 4

Common Pitfall: Assay Method Variability

  • High-performance liquid chromatography with tandem mass spectrometry (LC-MS/MS) is generally more accurate than immunoassays, but both are widely used 2, 4
  • Immunoassays can be affected by heterophilic antibodies, causing falsely elevated or decreased measurements 2
  • Some immunoassays, particularly older ones, significantly underestimate 25(OH)D2 levels (measuring only about 55% of actual values) 5

Result Interpretation Guidelines

  • Request results in ng/mL rather than nmol/L for consistency with most clinical guidelines 1
  • Be aware that total serum 25(OH)D may underestimate vitamin D status in African American patients due to differences in vitamin D binding protein, though bioavailable 25(OH)D may be similar across races 2

When to Retest After Supplementation

  • Wait at least 3 months after initiating vitamin D supplementation before retesting to allow serum concentrations to plateau and accurately reflect treatment response 2, 1
  • For intermittent dosing regimens (weekly or monthly), measure levels just prior to the next scheduled dose 1
  • Once the patient is stable on maintenance therapy, annual monitoring is sufficient 1

Who Should Be Tested

  • Do not perform population-wide screening 1
  • Test selectively in high-risk populations: patients with osteoporosis, malabsorption syndromes, chronic kidney disease, chronic liver disease, darker skin pigmentation, limited sun exposure, obesity, elderly/institutionalized individuals, or those on medications affecting vitamin D metabolism 1
  • For dark-skinned, veiled, elderly (≥65 years), or institutionalized individuals, you may supplement empirically with 800 IU daily without baseline testing 1

References

Guideline

Vitamin D Testing Guidelines

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Guideline

Vitamin D Testing Guidelines

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Blood biomarkers of vitamin D status.

The American journal of clinical nutrition, 2008

Research

Analytical validation of the Roche 25-OH Vitamin D Total assay.

Clinical chemistry and laboratory medicine, 2012

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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