To the Editor: In previous publications, we presented evidence that 25-dehydroxyvitamin D (25[OH]D) in serum behaves as a negative acute-phase reactant, ie, that its concentration decreases in the presence of inflammatory states.1,2 Low levels may thus reflect low vitamin D stores or inflammation, complicating the clinical interpretation of test results.
We have recently become aware of the mechanism underlying this phenomenon: less than 1% of circulating 25(OH)D exists in unbound form, and the majority is tightly bound to vitamin D binding protein, while 10% to 15% is bound to albumin. Both are negative acute-phase proteins.3–5 As the serum concentrations of these proteins decrease, so does that of 25(OH)D. Similarly, the positive acute-phase behavior of copper is explained by the fact that it is bound to ceruloplasmin, a positive acute-phase protein.6
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REFERENCES
- 1↵Antonelli M, Kushner I. Low serum levels of 25-hydroxyvitamin D accompany severe COVID-19 because it is a negative acute phase reactant. Am J Med Sci 2021; 362(3):333–335. doi:10.1016/j.amjms.2021.06.005
- 2↵Antonelli MJ, Kushner I, Epstein M. The constellation of vitamin D, the acute-phase response, and inflammation. Cleve Clin J Med 2023; 90(2):85–89. doi:10.3949/ccjm.90a.22048
- 3↵Yousefzadeh P, Shapses SA, Wang X. Vitamin D binding protein impact on 25-hydroxyvitamin D levels under different physiologic and pathologic conditions. Int J Endocrinol 2014; 2014:981581. doi:10.1155/2014/981581
- 4Dahl B, Schiødt FV, Gehrchen PM, Ramlau J, Kiaer T, Ott P. Gc-globulin is an acute phase reactant and an indicator of muscle injury after spinal surgery. Inflamm Res 2001; 50(1):39–43. doi:10.1007/s000110050722
- 5↵Liberman U, Bikle DD. Disorders in the action of vitamin D. In: Feingold KR, Anawalt B, Blackman MR, et al, eds. Endotext. South Dartmouth, MA: MDText.com, Inc.; 2023.
- 6↵Sattar N, Scott HR, McMillan DC, Talwar D, O’Reilly DS, Fell GS. Acute-phase reactants and plasma trace element concentrations in non-small cell lung cancer patients and controls. Nutr Cancer 1997; 28(3):308–312. doi:10.1080/01635589709514592
