Metabolomics & Nutrition VITD

Vitamin D Metabolites.

Comprehensive vitamin D status assessment including supply, bioavailability, and supplementation efficacy. Performed by high-performance liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS).

Quick Reference
Method
LC-MS/MS
Sample Types
DBS Serum Plasma
Analytes

4 metabolites

Quality Assurance

DEQAS Participant

Sample Reports Vitamin D Vitamin D Plus
Turnaround

3–5 working days

Enquire About This Test

What does this test assess?

This method provides a comprehensive assessment of the body's vitamin D supply, enabling clinicians and researchers to evaluate status, supplementation efficacy, and metabolic bioavailability through a multi-metabolite profile.

Clinical indications include:

  • Differential diagnosis of causes of rickets and osteomalacia, low-energy fractures unrelated to high-force trauma, and calcium-phosphate disorders
  • Monitoring of therapy and supplementation with vitamin D preparations
  • Diagnosis of hypovitaminosis, hypervitaminosis, and vitamin D toxicity
  • Intestinal malabsorption, nephrotic syndrome, and liver disease
  • Decreased muscle and bone mass
  • Patients treated with corticosteroids, antiepileptic drugs, or immunosuppressants

Measured metabolites

Analyte Also Known As Notes
25(OH)D3 Calcifediol, Calcidiol, 25-Hydroxy Vitamin D3 Primary marker of vitamin D3 status
25(OH)D2 25-Hydroxy Vitamin D2 Marker of vitamin D2 (plant-derived) intake
24,25(OH)₂D3 24,25-Dihydroxy Vitamin D3 Catabolic metabolite used to calculate bioavailability ratio
Epi-25(OH)D3 3-epi-25-Hydroxy Vitamin D3 Epimeric form with reduced biological activity. Measured but excluded from clinical interpretation to avoid false elevation of results
Total Vitamin D — Sum Reporting

The result is expressed as the sum of 25(OH)D2 and 25(OH)D3, providing the total 25(OH)D concentration. Additionally, the bioavailability coefficient is calculated from the ratio of 25(OH)D3 to its catabolite 24,25(OH)₂D3, indicating the balance between absorption/production and excretion processes.

About vitamin D

Vitamin D, discovered over 100 years ago, was initially associated primarily with the body's calcium-phosphate balance — rickets in children, and osteomalacia and osteoporosis in adults. The discovery of the vitamin D receptor (VDR) in the 1970s in most extraskeletal human cells initiated extensive research into its role across numerous tissues.

D3

Cholecalciferol — produced by animals via UV-B skin synthesis

D2

Ergocalciferol — produced by plants, algae, and fungi

4–6 mo

Months per year with negligible cutaneous synthesis at higher latitudes

The primary sources of vitamin D for humans are skin synthesis (UV-B exposure) and intestinal absorption. However, these sources are inherently limited. Geographical latitude significantly affects cutaneous synthesis — in many regions, effective vitamin D production is negligible for 4–6 months of the year. Even a healthy, varied diet cannot fully satisfy the body's demand, raising the need for targeted supplementation across all age groups.

Why is vitamin D important?

Vitamin D is involved in a broad range of physiological processes. It regulates calcium metabolism and adequate bone mineralisation, influences cell proliferation and differentiation in the immune system, modulates the renin-angiotensin-aldosterone system and insulin secretion, and has anti-inflammatory and antioxidant effects.

Key physiological roles
Calcium metabolism & bone mineralisation
Immune system cell differentiation
Renin-angiotensin-aldosterone regulation
Anti-inflammatory & antioxidant effects
Insulin secretion modulation
Nervous, muscular & cardiovascular function

Deficiency can be associated with the development of numerous conditions including osteoporosis, dental caries, depression, atherosclerosis, muscle pain, decreased concentration, and increased susceptibility to seasonal infections. Vitamin D deficiency during pregnancy can increase the risk of complications and directly impacts supply to the foetus.

Vitamin D toxicity

Overdose, although extremely rare, is a real risk in individuals taking very high doses. It leads primarily to hypercalcaemia and may manifest as nausea, vomiting, abdominal pain, dehydration, weight loss, and renal dysfunction.

Who is at risk of deficiency?

While routine screening is not indicated for the general healthy population (where established supplementation regimens are recommended), an increasing number of clinical situations require vitamin D monitoring and optimisation.

Conditions requiring monitoring
! Musculoskeletal disorders & reduced bone mass
! Digestion, absorption & mineral metabolism disorders
! Liver & kidney diseases
! Endocrine & cardiovascular disorders
! Autoimmune & metabolic diseases
! Malignant diseases

Equally important are cases of genetic hypersensitivity to vitamin D, resulting from mutations in genes encoding vitamin D metabolising enzymes. These mutations can cause disproportionately strong responses to standard supplementation, potentially leading to toxicity.

Vitamin D supply reference ranges

Total 25(OH)D concentration is used to assess vitamin D status. The following reference ranges are based on international endocrine society guidelines.

25(OH)D (ng/mL) Status Recommendation
0 – 20 Deficiency Start supplementation per current guidelines. Repeat test after 3 months. If below 10 ng/mL, consult physician for treatment of vitamin D deficiency.
20 – 30 Suboptimal Start or increase supplementation dose by 50%. Repeat test in 6 months. Note: while >20 ng/mL is considered sufficient for rickets prevention, maintaining 30–50 ng/mL is recommended for broader health benefits.
30 – 50 Optimal Continue current management. Considered optimal by most endocrine societies worldwide.
50 – 100 High Generally recommended to reduce dose by 50% or pause supplementation for 1–2 months. In some clinical situations, concentrations above 50 ng/mL may be advisable. Consult physician to discuss strategy.
> 100 Toxic Discontinue supplementation immediately. Retest 25(OH)D at monthly intervals. Toxic effects are associated with accompanying hypercalcaemia and hypercalciuria. Physician consultation required.

Vitamin D bioavailability ratio

The metabolite 24,25(OH)₂D3 is formed from 25(OH)D3 by the enzyme 24-hydroxylase. The ratio of 25(OH)D3 to 24,25(OH)₂D3 provides insight into supplementation efficacy and potential genetic variations in vitamin D metabolism.

25(OH)D3 : 24,25(OH)₂D3 Interpretation Recommendation
< 6.98 Resistance to supplementation Supplement only under medical supervision. Indicates increased 24-hydroxylase enzyme activity, which may contribute to resistance to vitamin D supplementation. In situations of low 25(OH)D concentrations, intake may be increased but must be supervised.
6.98 – 23.64 Optimal supplementation Continue supplementation per current guidelines. Indicates normal 24-hydroxylase activity, characteristic of the majority of the population. No action required if total 25(OH)D is normal. If deficient, follow standard supplementation guidelines.
> 23.64 Insufficient supplementation Supplement only under medical supervision. Most commonly caused by insufficient 25(OH)D concentration. May also indicate bone disease, renal dysfunction, or calcium homeostasis disorders. A small group of individuals carry mutations in CYP24A1 (impaired 24-hydroxylase) or SLC34A1 (excessive calcitriol synthesis), both of which increase the risk of hypervitaminosis D.
Note on 24,25(OH)₂D3

An increase in the concentration of 24,25(OH)₂D3 primarily indicates an increased concentration of the active form of vitamin D (calcitriol), but may also suggest ongoing bone regeneration processes (e.g., after a fracture).

Analytical technique

The test is performed using the isotopic dilution method and high-performance liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS).

The use of LC-MS/MS provides analytical capabilities not achievable with other techniques. It delivers high repeatability and accuracy of measurements and ensures that results are not influenced by interfering substances such as 3-epi-25(OH)D3 or biotin — a known source of interference in immunoassay-based methods.

Sample flexibility

This method can be performed on three sample types: serum, plasma, or dried blood spot (DBS). DBS collection enables remote sampling without venepuncture, making it ideal for home testing kits, clinical trials with decentralised logistics, and paediatric applications.

External quality assessment

Masdiag Laboratory participates in the Vitamin D External Quality Assessment Scheme (DEQAS), an international proficiency testing programme that evaluates the accuracy and reliability of 25(OH)D measurements across participating laboratories worldwide.

Testing process

From enquiry to results in a few simple steps — no clinic visit required.

1
Get in touch
Contact us to discuss your testing requirements
2
Collect your sample
Simple finger-prick onto a dried blood spot card — at home or in clinic
3
Post to our lab
DBS cards are stable at room temperature — ship by regular post worldwide
4
Receive results
Results delivered within 3–5 working days of sample receipt

Where this test is available

This test is available to healthcare professionals, wellness brands, clinics, and research institutions worldwide. We currently serve partners in:

  • Europe (EU & non-EU)
  • United Kingdom
  • Asia & Southeast Asia
  • Australia & New Zealand
  • United States

Whether you need testing services for your patients, white-label kits for your brand, or method transfer to your own laboratory — get in touch to discuss how we can work together.

Literature

  1. Rusińska A, Płudowski P, Walczak M, et al. “Vitamin D Supplementation Guidelines for General Population and Groups at Risk of Vitamin D Deficiency in Poland — 2018 Update.” Front Endocrinol (Lausanne), 2018, 9:246. doi:10.3389/fendo.2018.00246
  2. Galior K, et al. “Development of Vitamin D Toxicity from Overcorrection of Vitamin D Deficiency: A Review of Case Reports.” Nutrients, 2018, 10, 953. doi:10.3390/nu10080953
  3. Botelho J, et al. “Vitamin D Deficiency and Oral Health: A Comprehensive Review.” Nutrients, 2020, 12, 1471. doi:10.3390/nu12051471
  4. Bi WG, et al. “Maternal–Fetal Impact of Vitamin D Deficiency: A Critical Review.” Maternal and Child Health Journal, 2015, 19, 94–101. doi:10.1007/s10995-014-1499-7
  5. Rai V, Agrawal DK. “Vitamin D deficiency and risk of cardiovascular diseases: a narrative review.” Clinical Hypertension, 2018, 24, 9. doi:10.1186/s40885-018-0094-4
  6. Anglin RES, et al. “Vitamin D deficiency and depression in adults: systematic review and meta-analysis.” The British Journal of Psychiatry, 2013, 202, 2. doi:10.1192/bjp.bp.111.106666

Frequently Asked Questions

What does the vitamin D test measure?

This test measures four vitamin D metabolites from a single sample: 25(OH)D3 (the primary marker of vitamin D3 status), 25(OH)D2 (reflecting plant-derived vitamin D2 intake), 24,25(OH)2D3 (a catabolic metabolite used to calculate bioavailability), and 3-epi-25(OH)D3 (an epimeric form with reduced biological activity that is excluded from clinical interpretation). This makes it one of the most comprehensive vitamin D panels available from a dried blood spot.

Why is testing vitamin D important?

Vitamin D deficiency affects bone health, immune function, mood, cardiovascular health, and muscle strength. Deficiency is widespread globally, particularly in northern latitudes where UV-B exposure is limited for several months of the year. Both deficiency and excess can be harmful, making accurate measurement essential for safe supplementation. Testing also reveals your bioavailability ratio, which can identify genetic variations affecting how your body processes vitamin D.

How is the sample collected?

The test uses a simple finger-prick to collect a few drops of blood onto a dried blood spot (DBS) card. You can do this at home or in a clinic — no venous blood draw is needed. The DBS card is stable at room temperature and can be posted to our laboratory by regular mail from anywhere in the world. Serum and plasma samples are also accepted.

How long does it take to get results?

Results are typically delivered within 3 to 5 working days from the time your sample arrives at our laboratory. The analysis is performed by LC-MS/MS, which provides superior accuracy compared to immunoassay methods and eliminates interference from biotin and the 3-epi-25(OH)D3 epimer.

What is a healthy vitamin D level?

A total 25(OH)D concentration of 30 to 50 ng/mL (75 to 125 nmol/L) is generally considered optimal by most endocrine societies. Below 20 ng/mL is classified as deficient, while 20 to 30 ng/mL is suboptimal. Levels above 100 ng/mL may indicate toxicity. Your healthcare provider should interpret your results in the context of your clinical situation, as some conditions may warrant higher or lower target ranges.

Which countries is this test available in?

Masdiag's vitamin D test is available worldwide through our partner network. We currently serve healthcare professionals, wellness brands, and clinics in Europe, the United Kingdom, Asia, Australia, New Zealand, and the United States. Contact us to discuss testing services, white-label kits, or method transfer to your laboratory.

Interested in this method?

Whether you need testing services, method transfer, or white-label kit development — we'd love to hear from you.