Letter to the Editor

Why 25-dehydroxyvitamin D is a negative acute-phase reactant

Maria J. Antonelli, MD, Irving Kushner, MD and Murray Epstein, MD, FASN, FACP
Cleveland Clinic Journal of Medicine September 2023, 90 (9) 535; DOI: https://doi.org/10.3949/ccjm.90c.09001

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

REFERENCES

  1. ↵
    1. Antonelli M,
    2. 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
    OpenUrlCrossRef
  2. ↵
    1. Antonelli MJ,
    2. Kushner I,
    3. 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
    OpenUrlFREE Full Text
  3. ↵
    1. Yousefzadeh P,
    2. Shapses SA,
    3. 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
    OpenUrlCrossRef
    1. Dahl B,
    2. Schiødt FV,
    3. Gehrchen PM,
    4. Ramlau J,
    5. Kiaer T,
    6. 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
    OpenUrlCrossRefPubMed
  5. ↵
    1. Feingold KR,
    2. Anawalt B,
    3. Blackman MR, et al.
    1. Liberman U,
    2. 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. ↵
    1. Sattar N,
    2. Scott HR,
    3. McMillan DC,
    4. Talwar D,
    5. O’Reilly DS,
    6. 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
    OpenUrlCrossRefPubMed
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