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. 2023 Jul 5;69(7):718-723.
doi: 10.1093/clinchem/hvad050.

The Vitamin D Metabolite Ratio (VMR) is a Biomarker of Vitamin D Status That is Not Affected by Acute Changes in Vitamin D Binding Protein

Anushree Dugar  1 , Andrew N Hoofnagle  2 , Amber P Sanchez  3 , David M Ward  3 , Jody Corey-Bloom  4 , Jonathan H Cheng  3   5 , Joachim H Ix  3   5 , Charles Ginsberg  3
Affiliations

The Vitamin D Metabolite Ratio (VMR) is a Biomarker of Vitamin D Status That is Not Affected by Acute Changes in Vitamin D Binding Protein

Anushree Dugar et al. Clin Chem. .

Erratum in

Abstract

Background: 25-hydroxyvitamin D[25(OH)D] may be a poor marker of vitamin D status due to variability in levels of vitamin D binding protein (VDBP). The vitamin D metabolite ratio (VMR) is the ratio of 24,25-dihydroxyvitamin D[24,25(OH)2D3] to 25(OH)D3 and has been postulated to reflect vitamin D sufficiency independent of variability in VDBP. Therapeutic plasma exchange (TPE) is a procedure that removes plasma, including VDBP, and may lower bound vitamin D metabolite concentrations. Effects of TPE on the VMR are unknown.

Methods: We measured 25(OH)D, free 25(OH)D, 1,25-dihydroxyvitamin D[1,25(OH)2D], 24,25(OH)2D3, and VDBP in persons undergoing TPE, before and after treatment. We used paired t-tests to assess changes in these biomarkers during a TPE procedure.

Results: Study participants (n = 45) had a mean age of 55 ± 16 years; 67% were female; and 76% were white. Compared to pretreatment concentrations, TPE caused a significant decrease in total VDBP by 65% (95%CI 60,70%), as well as all the vitamin D metabolites-25(OH)D by 66% (60%,74%), free 25(OH)D by 31% (24%,39%), 24,25(OH)2D3 by 66% (55%,78%) and 1,25(OH)2D by 68% (60%,76%). In contrast, there was no significant change in the VMR before and after a single TPE treatment, with an observed mean 7% (-3%, 17%) change in VMR.

Conclusions: Changes in VDBP concentration across TPE parallel changes in 25(OH)D, 1,25(OH)2D, and 24,25(OH)2D3, suggesting that concentrations of these metabolites reflect underlying VDBP concentrations. The VMR is stable across a TPE session despite a 65% reduction in VDBP. These findings suggest that the VMR is a marker of vitamin D status independent of VDBP levels.

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Conflict of interest statement

Upon manuscript submission, all authors completed the author disclosure form. Disclosures and/or potential conflicts of interest:

Figures

Fig. 1.
Fig. 1.
The VMR is hypothetically independent of VDBP concentrations. The effects of VDBP on 25(OH)D (in the denominator) and 24,25(OH)2D3 (in the numerator) hypothetically cancel out in the VMR.
Fig. 2.
Fig. 2.
Changes in vitamin D metabolites, VDBP, and VMR during TPE (N = 45). Acute reductions in VDBP are associated with similar reductions in all vitamin D metabolites but not the VMR. Abbreviations: 25D, 25-hydroxyvitamin D; Free D, Free 25-hydroxyvitamin D; 24,25D3, 24,25-dihydroxyvitamin D3; 1,25D, 1,25-dihydroxyvitamin D.
See this image and copyright information in PMC

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