Vitamin D Is Bound to This Specific Protein for Transport

October 25, 2025 •

3 min read

Approximately 85–90% of all circulating vitamin D metabolites are bound to a specific carrier protein in the bloodstream. This vital transport protein, known as Vitamin D-Binding Protein (DBP), is responsible for carrying vitamin D throughout the body and controlling its availability to various tissues.

Quick Summary

The majority of vitamin D in the bloodstream is transported by Vitamin D-Binding Protein (DBP), also known as Gc-globulin. This binding regulates the vitamin's bioavailability, protects it from degradation, and facilitates its delivery to target organs like the kidneys and liver for processing and activation.

Key Points

Primary Carrier: The main protein that binds and transports vitamin D and its metabolites in the bloodstream is called Vitamin D-Binding Protein (DBP), or Gc-globulin.
Regulates Bioavailability: DBP controls the amount of 'free' (unbound) and active vitamin D available to various tissues, acting as a crucial regulator of the vitamin's biological effects.
Protective Reservoir: By binding to vitamin D, DBP creates a circulating reservoir that protects the vitamin from rapid degradation and urinary loss, extending its half-life.
Genetic Influence: Genetic variations in the DBP gene can significantly influence the protein's concentration and its affinity for vitamin D, impacting an individual's functional vitamin D status.
Kidney Reabsorption: The DBP-vitamin D complex is filtered by the kidneys but is efficiently reabsorbed by the receptor megalin in the proximal tubules, preventing its loss.
Other Roles: Apart from transporting vitamin D, DBP also plays important roles in the immune system, fatty acid transport, and scavenging cellular actin released during tissue damage.

What is Vitamin D-Binding Protein (DBP)?

Vitamin D-Binding Protein (DBP), also known as Gc-globulin, is a plasma protein primarily produced by the liver that transports vitamin D and its metabolites. This binding is crucial because it makes vitamin D less susceptible to degradation and prevents its rapid clearance from the bloodstream. DBP carries forms like 25-hydroxyvitamin D [25(OH)D] and the active 1,25-dihydroxyvitamin D [1,25(OH)2D].

The Multifaceted Role of DBP

DBP has several functions beyond vitamin D transport, including:

Actin scavenging: DBP binds to actin released from damaged tissues, preventing it from causing vascular problems.
Immune modulation: It acts as a co-chemotactic agent and can be converted into a macrophage-activating factor.
Fatty acid transport: DBP also binds and transports fatty acids.

How DBP Governs Vitamin D Bioavailability

Most vitamin D in circulation is bound to DBP, with a small amount bound to albumin and a tiny fraction in a 'free' state. The "free hormone hypothesis" suggests only this unbound vitamin D can easily access cell receptors. DBP acts as a reservoir, providing a regulated supply of vitamin D and protecting it from breakdown. It facilitates delivery to organs like the kidneys for activation. Cells, particularly in the kidneys, take up the DBP-vitamin D complex via a process involving the megalin receptor.

The Genetic Polymorphism of DBP and Its Consequences

DBP has significant genetic diversity, with variants affecting its concentration and binding affinity for vitamin D metabolites. These variants differ among populations, influencing individual responses to vitamin D levels.

Impact of Genetic Variants on Vitamin D and Health


Feature	Gc1F Variant	Gc1S Variant	Gc2 Variant
Associated DBP Level (Homozygote)	Lowest	Highest	Intermediate
Affinity for 25(OH)D	Highest	Intermediate	Lowest
Vitamin D Bioavailability	Lower total, potentially higher free	Higher total, potentially lower free	Lower total, potentially adequate free
Commonality in Population	More common in African descent	Present in various populations	More common in Caucasians

Genetic differences mean that total vitamin D levels may not always reflect the amount of free, functional vitamin D.

Clinical Significance of DBP

DBP levels can change in certain health states, affecting vitamin D interpretation.

Liver Disease: Reduced liver function can lower DBP levels.
Kidney Disease: Conditions like nephrotic syndrome can cause DBP loss in urine. Kidney reabsorption involving megalin is important here.
Pregnancy: DBP levels increase during pregnancy due to hormonal changes.

These situations can lead to low total vitamin D, but free vitamin D levels may not be as affected.

Conclusion

Vitamin D is primarily bound to Vitamin D-Binding Protein (DBP), a protein vital for its transport, bioavailability, and protection in the body. DBP regulates the amount of free, active vitamin D available to tissues. Genetic variations in DBP and changes in its levels during certain conditions mean that total vitamin D measurements alone may not fully capture a person's functional vitamin D status. Beyond transport, DBP is involved in immune function and other processes. Understanding DBP's complex role is important for evaluating vitamin D status and its impact on health.

For additional scientific details on Vitamin D-Binding Protein, refer to the Endocrine Reviews monograph.

Frequently Asked Questions

The primary protein that binds to vitamin D in the blood is called Vitamin D-Binding Protein (DBP). It is also known as Gc-globulin.

DBP transports vitamin D and its metabolites in the circulation, regulates the bioavailability of free vitamin D to target tissues, and acts as a reservoir to prevent rapid degradation and loss.

Since DBP carries most vitamin D, its levels can affect the accuracy of total vitamin D measurements. For example, in liver disease or pregnancy, altered DBP levels can lead to a misrepresentation of a person's true functional vitamin D status.

According to the "free hormone hypothesis," only the small fraction of vitamin D that is free and unbound is biologically active and accessible to cells. However, DBP-bound vitamin D is still crucial for maintaining stable reserves.

Studies in DBP-null mice and rare human cases show very low total vitamin D levels, but often normal calcium balance. This suggests that other transport mechanisms, like albumin, can compensate, though these individuals may be more susceptible to dietary vitamin D deficiency.

Yes, variations in DBP levels and its binding affinity, which can be influenced by genetic polymorphisms, have been linked to differences in bone mineral density and fracture risk in some studies. DBP also plays a role in activating osteoclasts for bone resorption.

DBP levels can be influenced by conditions that affect the liver, such as liver disease, or conditions causing protein loss, like nephrotic syndrome. Hormonal changes, such as those during pregnancy, can also increase DBP levels.