What is the conversion of vitamin D2?

November 27, 2025 •

3 min read

Did you know that vitamin D from supplements or food is biologically inactive until it undergoes two critical enzymatic conversions in the body? This process, which clarifies what is the conversion of vitamin D2, transforms the inert prohormone, ergocalciferol, into its powerful, active hormonal form.

Quick Summary

Vitamin D2 (ergocalciferol) is converted in a two-step process: first, hydroxylation in the liver to 25-hydroxyvitamin D2, then a second hydroxylation in the kidneys to the active form, calcitriol.

Key Points

Two-Step Process: Vitamin D2 (ergocalciferol) requires two hydroxylation steps, occurring in the liver and kidneys, to become biologically active.
Liver Conversion: The liver enzyme 25-hydroxylase (CYP2R1) converts vitamin D2 into 25-hydroxyvitamin D2, the main circulating form.
Kidney Activation: The kidney enzyme 1-alpha-hydroxylase (CYP27B1) performs the final conversion to the active hormone, calcitriol (1,25-dihydroxyvitamin D2).
Differences from D3: Vitamin D3 may be more potent at raising serum levels of 25-hydroxyvitamin D due to differences in metabolism and affinity for binding proteins,.
Active Form's Function: Active vitamin D2 (calcitriol) regulates calcium and phosphate absorption in the intestines and plays a vital role in bone health.
Regulation of Conversion: The renal activation is tightly controlled by hormones like PTH and FGF23, which ensure appropriate calcitriol levels.

The Two-Step Conversion Process

Vitamin D2, or ergocalciferol, is a prohormone requiring metabolic activation to perform its functions in regulating calcium and phosphate balance and supporting bone health. The conversion involves two enzymatic steps in different organs.

Step 1: Hepatic Hydroxylation in the Liver

Ingested vitamin D2 travels to the liver where the enzyme 25-hydroxylase, mainly CYP2R1, adds a hydroxyl group to the 25th carbon. This produces 25-hydroxyvitamin D2 (ercalcidiol).

Enzyme: 25-hydroxylase (CYP2R1)
Location: Liver
Resulting Molecule: 25-hydroxyvitamin D2 (Ercalcidiol)

25-hydroxyvitamin D2 is the primary circulating form and is measured to assess vitamin D status. It is still largely inactive at this stage.

Step 2: Renal Hydroxylation in the Kidneys

25-hydroxyvitamin D2 is transported to the kidneys, where the enzyme 1-alpha-hydroxylase (CYP27B1) adds another hydroxyl group to the first carbon. This final step yields 1,25-dihydroxyvitamin D2 (ercalcitriol), the active hormonal form.

Enzyme: 1-alpha-hydroxylase (CYP27B1)
Location: Kidneys (primarily)
Resulting Molecule: 1,25-dihydroxyvitamin D2 (Ercalcitriol), the active hormone

The activity of 1-alpha-hydroxylase is regulated by factors like parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) to manage calcium and phosphate levels.

Vitamin D2 vs. Vitamin D3 Conversion: A Comparison

The conversion of vitamin D2 and D3 share similarities but differ in efficiency and metabolism. The table below highlights key differences.


Feature	Vitamin D2 (Ergocalciferol)	Vitamin D3 (Cholecalciferol)
Natural Source	Plants and yeast	Sunlight on skin and animal-based foods
Affinity for DBP	Lower affinity for vitamin D-binding protein	Higher affinity for vitamin D-binding protein
Circulating Half-Life	Shorter circulating half-life for 25(OH)D2	Longer circulating half-life for 25(OH)D3
Conversion Efficacy	Less effective than D3 at raising and maintaining serum 25(OH)D levels,	More effective than D2 at raising serum 25(OH)D levels, especially with bolus doses,
Final Active Form	1,25-dihydroxyvitamin D2 (Ercalcitriol)	1,25-dihydroxyvitamin D3 (Calcitriol)
Efficacy of Active Form	May have reduced ability to regulate some cellular events compared to 1,25(OH)2D3	Generally considered the standard for hormonal function

Regulation and Factors Influencing Conversion

Vitamin D metabolism is tightly controlled to maintain appropriate levels. Factors regulating the kidney's 1-alpha-hydroxylase include:

Parathyroid Hormone (PTH): Stimulates 1-alpha-hydroxylase to increase active calcitriol when calcium is low.
Fibroblast Growth Factor 23 (FGF23): Inhibits 1-alpha-hydroxylase to prevent excessive calcium and phosphate levels.
Serum Calcium and Phosphate: High levels suppress calcitriol production.
Dosage Regimen: Dosing frequency might affect the D2 vs. D3 efficacy difference, with daily dosing showing less difference than bolus doses.
Body Mass Index (BMI): Higher BMI may influence the response to supplementation.

The Role of Active Vitamin D2

Active vitamin D2 (ercalcitriol) binds to the vitamin D receptor (VDR) and regulates gene expression. Key functions include:

Intestinal Calcium Absorption: Increases calcium uptake in the intestines.
Bone Health: Maintains calcium and phosphate levels for bone mineralization.
Inactivation Pathway: Stimulates CYP24A1, an enzyme that breaks down vitamin D metabolites, preventing buildup.

Storage and Excretion

Excess vitamin D is stored in fat, liver, and muscle. Vitamin D and its metabolites are primarily excreted in bile and feces, with some in urine.

Conclusion

Vitamin D2 undergoes a vital two-step conversion in the liver and kidneys to become active 1,25-dihydroxyvitamin D2. This process, involving specific enzymes and tight regulation by hormones and mineral levels, is crucial for calcium homeostasis and bone health. Although vitamin D3 may be more effective in increasing circulating vitamin D levels, both forms are utilized by the body. Understanding this pathway clarifies what is the conversion of vitamin D2 and its role in health.

For more information on vitamin D metabolism, refer to the NIH Office of Dietary Supplements: Vitamin D - Health Professional Fact Sheet.

Frequently Asked Questions

The chemical name for vitamin D2 is ergocalciferol. It is derived from the plant sterol ergosterol after ultraviolet irradiation and is used in dietary supplements and fortified foods.

Once converted in the liver to 25-hydroxyvitamin D2, the body stores this metabolite in fat and muscle tissue for later use. However, some studies suggest that the stored 25(OH)D2 has a shorter circulating half-life compared to 25(OH)D3,.

The liver is the site of the first and essential conversion step. There, vitamin D2 is hydroxylated to 25-hydroxyvitamin D2 by the enzyme 25-hydroxylase (CYP2R1).

The kidney contains the enzyme 1-alpha-hydroxylase (CYP27B1), which converts 25-hydroxyvitamin D2 into the final, biologically active form, 1,25-dihydroxyvitamin D2 (ercalcitriol).

Studies suggest that vitamin D3 is more effective than vitamin D2 at raising and maintaining serum 25-hydroxyvitamin D concentrations, especially with high-dose bolus supplementation,. However, both are metabolized similarly to produce active calcitriol and are considered equivalent by some dietary guidelines.

25-hydroxyvitamin D (25[OH]D) is the major circulating form of vitamin D in the body, produced in the liver from both D2 and D3. It is the best clinical indicator of a person's overall vitamin D status and is what clinicians measure in blood tests.

The conversion in the kidney is tightly regulated by parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), and the body's levels of calcium and phosphate.

The body has a built-in feedback mechanism to prevent toxicity. The enzyme 24-hydroxylase (CYP24A1) catabolizes both 25(OH)D and 1,25(OH)2D, initiating a process that leads to their inactivation and eventual excretion.