Ann Lab Med.  2017 Jan;37(1):34-38. 10.3343/alm.2017.37.1.34.

Clinical Utility of Measurement of Vitamin D-Binding Protein and Calculation of Bioavailable Vitamin D in Assessment of Vitamin D Status

• Kim HJ
• Ji M
• Song J
• Moon HW
• Hur M
• Yun YM

• KMID: 2373611
• DOI: http://doi.org/10.3343/alm.2017.37.1.34

Abstract

BACKGROUND
The associations of vitamin D deficiency with various clinical conditions highlighted the importance of vitamin D testing. Currently, clinicians measure only the total 25-hydroxyvitamin D [25(OH)D] concentration, regardless of its bioavailability. We aimed to determine the effect of vitamin D-binding protein (VDBP) on 25(OH)D bioavailability.
METHODS
Serum samples were collected from 60 healthy controls, 50 pregnant women, and 50 patients in intensive care units (ICUs). Total 25(OH)D was quantified by liquid chromatography with tandem mass spectrometry, and VDBP levels were determined by using an ELISA kit (R&D Systems, USA). The bioavailable 25(OH)D levels were calculated by using total 25(OH)D, VDBP, and albumin concentrations.
RESULTS
In comparison with healthy controls, the total 25(OH)D concentration was significantly lower in ICU patients (median, 11.65 vs 18.25 ng/mL; P<0.00001), but no significant difference was noted between pregnant women (18.25 ng/mL) and healthy controls. The VDBP level was significantly lower in ICU patients (95.58 vs 167.18 µg/mL, P=0.0002) and higher in pregnant women (225.01 vs 167.18 µg/mL, P=0.008) compared with healthy controls. Nonetheless, the calculated bioavailable 25(OH)D levels of ICU patients and pregnant women were significantly lower than those of healthy controls (1.97 and 1.93 ng/mL vs 2.56 ng/mL; P=0.0073 and 0.0027).
CONCLUSIONS
A single marker of the total 25(OH)D level is not sufficient to accurately evaluate vitamin D status, especially in pregnant women. In cases where VDBP concentrations may be altered, VDBP measurements and bioavailable 25(OH)D calculations may help to determine vitamin D status accurately.

Keyword

Vitamin D-binding protein; 25-Hydroxyvitamin D; Bioavailability

MeSH Terms

Adult
Aged
Chromatography, High Pressure Liquid
Enzyme-Linked Immunosorbent Assay
Female
Humans
Intensive Care Units
Male
Middle Aged
Pregnancy
Pregnant Women
Serum Albumin/analysis
Tandem Mass Spectrometry
Vitamin D/*blood
Vitamin D-Binding Protein/*blood
Serum Albumin
Vitamin D
Vitamin D-Binding Protein

Figure

• 

  Fig. 1 Comparison of total 25-hydroxyvitamin D [25(OH)D], vitamin D binding protein (VDBP), and calculated bioavailable 25(OH)D in the three study groups. (A) The total 25(OH)D level in intensive care unit (ICU) patients (median, interquartile range: 11.65, 7.86-14.87 ng/mL) was significantly lower than that in healthy controls (18.25, 13.48-23.78 ng/mL) or in pregnant women (18.25, 13.98-25.24 ng/mL). (B) The VDBP level in pregnant women (225.01, 130.24-422.92 µg/mL) was significantly higher, and the VDBP level in ICU patients (95.58, 61.15-167.34 µg/mL) was significantly lower than that in healthy controls (167.18, 105.99-257.70 µg/mL). (C) The calculated bioavailable 25(OH)D levels of ICU patients (1.97, 1.48-3.15 ng/mL) and pregnant women (1.93, 1.03-3.41 ng/mL) were significantly lower than those in healthy controls (2.56, 1.95-4.22 ng/mL). P values were calculated by the Mann-Whitney test. Two dashed lines denote vitamin D deficiency and severe vitamin D deficiency. The arrowheads and dots represent the outside value (>1.5× interquartile ranges) and far-out value (>3× interquartile ranges), respectively. The horizontal lines represent maximum and minimum values, except for the outside value and far-out value.

• 

  Fig. 2 Comparison of total 25-hydroxyvitamin D [25(OH)D], vitamin D-binding protein (VDBP), and calculated bioavailable 25(OH)D by gestational stage. (A) Total 25(OH)D levels were not significantly different between the 1st and 2nd and 3rd trimesters (median, interquartile range: 1st trimester: 18.20, 15.07-23.87 ng/mL; 2nd and 3rd trimesters: 18.30, 13.75-25.70 ng/mL). (B) VDBP levels during the 2nd and 3rd trimesters were significantly higher than those during the 1st trimester (1st trimester: 102.20, 84.75-259.90 µg/mL, 2nd and 3rd trimesters: 273.65, 163.75-453.98 µg/mL). (C) The calculated bioavailable 25(OH)D level in the 2nd and 3rd trimesters was significantly lower than that in the 1st trimester (1st trimester: 4.19, 2.09-5.67 ng/mL; 2nd and 3rd trimesters, 1.73, 0.90-2.43 ng/mL). P values were calculated by the Mann-Whitney test. Two dashed lines denote vitamin D deficiency and severe vitamin D deficiency. The arrowheads and dots represent the outside value (>1.5× interquartile ranges) and far-out value (>3× interquartile ranges), respectively. The horizontal lines represent the maximum and minimum values, except for the outside value and far-out value.

Reference

1. DeLuca HF. Overview of general physiologic features and functions of vitamin D. Am J Clin Nutr. 2004; 80(6 Suppl):S1689–S1696.

2. Holick MF. Vitamin D deficiency. N Engl J Med. 2007; 357:266–281. PMID: 17634462.

3. Bhan I, Powe CE, Berg AH, Ankers E, Wenger JB, Karumanchi SA, et al. Bioavailable vitamin D is more tightly linked to mineral metabolism than total vitamin D in incident hemodialysis patients. Kidney Int. 2012; 82:84–89. PMID: 22398410.

4. Bikle DD, Gee E, Halloran B, Kowalski MA, Ryzen E, Haddad JG. Assessment of the free fraction of 25-hydroxyvitamin D in serum and its regulation by albumin and the vitamin D-binding protein. J Clin Endocrinol Metab. 1986; 63:954–959. PMID: 3745408.

5. Bikle DD, Siiteri PK, Ryzen E, Haddad JG. Serum protein binding of 1,25-dihydroxyvitamin D: a reevaluation by direct measurement of free metabolite levels. J Clin Endocrinol Metab. 1985; 61:969–975. PMID: 3840175.

6. Chun RF. New perspectives on the vitamin D binding protein. Cell Biochem Funct. 2012; 30:445–456. PMID: 22528806.

7. Bhan I. Vitamin D binding protein and bone health. Int J Endocrinol. 2014; 2014:561214. PMID: 24987416.

8. Heijboer AC, Blankenstein MA, Kema IP, Buijs MM. Accuracy of 6 routine 25-hydroxyvitamin D assays: influence of vitamin D binding protein concentration. Clin Chem. 2012; 58:543–548. PMID: 22247500.

9. Schwartz JB, Lai J, Lizaola B, Kane L, Markova S, Weyland P, et al. A comparison of meassured and calculated and free 25(OH) vitamin D levels in clinical populations. J Clin Endocrinol Metab. 2014; 99:1631–1637. PMID: 24483159.

10. Arnaud J, Constans J. Affinity differences for vitamin D metabolites associated with the genetic isoforms of the human serum carrier protein (DBP). Hum Genet. 1993; 92:183–188. PMID: 8370586.

11. Thacher TD, Clarke BL. Vitamin D insufficiency. Mayo Clin Proc. 2011; 86:50–60. PMID: 21193656.

12. Lappe JM, Travers-Gustafson D, Davies KM, Recker RR, Heavey RP. Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Am J Clin Nutr. 2007; 85:1586–1591. PMID: 17556697.

13. Mitchell D. The relationship between vitamin D and cancer. Clin J Oncol Nurs. 2011; 15:557–560. PMID: 21951742.

14. Mann MC, Hollenberg MD, Hanley DA, Ahmed SB. Vitamin D, the autonomic nervous system, and cardiovascular risk. Physiol Rep. 2015; 3:e12349. PMID: 25902783.

15. Garlanad CF, Garland FC, Gorham ED, Lipkin M, Newmark H, Mohr SB, et al. The role of vitamin D in cancer prevention. Am J Public Health. 2006; 96:252–261. PMID: 16380576.

16. Ponsonby AL, McMichael A, van der Mei I. Ultraviolet radiation and autoimmune disease: insights from epidemiological research. Toxicology. 2002; 181-182:71–78. PMID: 12505287.

17. McGrath J, Selten JP, Chant D. Long-term trends in sunshine duration and its association with schizophrenia birth rates and age at first registration - data from Australia and the Netherlands. Schizophr Res. 2002; 54:199–212. PMID: 11950544.

18. Iglar PJ, Hogan KJ. Vitamin D status and surgical outcomes: a systematic review. Patient Saf Surg. 2015; 9:14–23. PMID: 25926889.

19. Cleal JK, Day PE, Simner CL, Barton SJ, Mahon PA, Inskip HM, et al. Placental amino acid transport may be regulated by maternal vitamin D and vitamin D-binding protein: results from the Southampton Women's Survey. Br J Nutr. 2015; 113:1903–1910. PMID: 25940599.

20. Shao H, Tao M, Fan Y, Jing J, Lu J. Vitamin D levels and other factors related to bone mineral density during pregnancy. Aust N Z J Obstet Gynaecol. 2012; 52:571–575. PMID: 23003672.

21. Bouillon R, Van Assche FA, Van Baelen H, Heyns W, De Moor P. Influence of the vitamin-D binding protein on the serum concentration of 1,25-dihydroxyvitamin D3. Significance of the free 1,25-dihydroxyvitamin D3 concentration. J Clin Invest. 1981; 67:589–596. PMID: 6894152.

22. Powe CE, Evans MK, Wenger J, Zonderman AB, Berg AH, Nalls M, et al. Vitamin D-binding protein and vitamin D status of black Americans and white Americans. N Engl J Med. 2013; 369:1991–2000. PMID: 24256378.

23. Bikle DD, Gee E, Halloran B, Haddad JG. Free 1,25-dihydroxy vitamin D levels in serum from normal subject, pregnant subjects, and subjects with liver disease. J Clin Invest. 1984; 74:1966–1971. PMID: 6549014.

24. Pop LC, Shapses SA, Chang B, Sun W, Wang X. Vitamin D-binding protein in healthy pre- and postmenopausal women: relationship with estradiol concentrations. Endocr Pract. 2015; 21:936–942. PMID: 26121448.

25. Kamboh MI, Ferrell RE. Ethnic variation in vitamin D-binding protein (GC): a review of isoelectric focusing studies in human populations. Hum Genet. 1986; 72:281–293. PMID: 3516862.