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There's a relatively new player on the vitamin D playing field, and it's likely to be the subject of much research in the future.
Researchers have become more interested in vitamin D binding protein and how it impacts not only vitamin D bioavailability, but also clinical outcomes such as bone density and fracture.
Vitamin D binding protein is the primary vitamin D carrier protein, binding some 85% to 90% of the total 25(OH)D in circulation (about 15% to 10% of vitamin D is bound by albumin, and then the smallest fraction -- some 1% -- is actually free and bioavailable vitamin D; together, these three types make up the total vitamin D level).
When the vitamin is tied up with its binding protein, it is unavailable to the body's tissues, so high levels of this protein could also play a role in the effects of vitamin D deficiency, some researchers say.
For example, last November, researchers reporting in the New England Journal of Medicine found that although blacks have more vitamin D deficiency than whites when measuring total 25(OH)D levels, they have similar amounts of bioavailable levels of vitamin D -- because they have a polymorphism in the vitamin D-binding protein gene that keeps levels of the protein low.
That could help explain why despite the lower total levels, blacks experience fewer of the complications of deficiency, such as fracture, those authors said.
Xiangbing Wang, MD, of Rutgers Robert Wood Johnson Medical School in New Jersey, who presented a poster on vitamin D binding protein at the Endocrine Society meeting in Chicago in June, told MedPage Today that the accumulating literature is suggesting that "it's not only the total vitamin D level, but the free and bioavailable vitamin D level that is important."
What could that mean for clinical practice? Nothing right now, Wang says. The vitamin D binding protein assays are too expensive, but that could change in the next few years, as some companies have become interested in providing the service commercially, he said.
Although the work is still far from clinical implementation, Wang says clinicians don't have to just look at total vitamin D levels to determine if a patient needs treatment.
"When you get a low vitamin D level and you can't measure vitamin D binding protein, you can measure calcium and parathyroid hormone levels," he says. "If you have low vitamin D but calcium and PTH are okay, it's most likely you don't have to treat [the deficiency]."
Wang was recently a guest editor for a special issue of the International Journal of Endocrinology on vitamin D biding protein, and his work has shown some interesting associations. For instance, one recent paper showed that vitamin D binding protein fell as patients aged, which "may be some protective mechanism against vitamin D deficiency, making vitamin D more bioavailable," he said.
Still, it will take much more research before clinicians start calculating vitamin D binding protein levels in their deficiency screens.