ABSTRACT
25-Hydroxyvitamin D (25OHD) and 1,25-dihydroxyvitamin D (1,25(OH)2D) need to be bound to carrier proteins to be transported to their target cells. The majority of either 25OHD or 1,25(OH)2D is bound to vitamin D-binding protein (DBP), a smaller fraction is bound to albumin and only very small amounts of 25OHD or 1,25(OH)2D are free. Albumin-bound 25OHD or 1,25(OH)2D is relatively easily available after dissociation from albumin. Thus, the sum of free and albumin-bound forms is called bioavailable 25OHD and bioavailable 1,25(OH)2D. Total 25OHD and 1,25(OH)2D are defined as the sum of free, albumin-bound and DBP-bound 25OHD and 1,25(OH)2D, respectively. This cross-sectional study in 427 pregnant women compared the correlation of the six vitamin D compounds with biomarkers of bone health, lipid metabolism, kidney function, endocrine parameters, and group B water-soluble vitamins. Among the 25OHD metabolites analysed, total 1,25(OH)2D showed clearly the best correlation with calcium, bone-specific alkaline phosphatase, adiponectin, LDL, HDL, urea, thyroxine, and group B water-soluble vitamins. When comparing the three 25OHD metabolites, both free 25OHD and bioavailable 25OHD showed overall good correlations with calcium, bone-specific alkaline phosphatase, adiponectin, LDL, HDL, urea, thyroxine, triiodothyronine, and group B water-soluble vitamins, The correlations of 1,25(OH)2D and 25OHD metabolites went always in opposite directions. Only PTH correlates always inversely with all six vitamin D compounds. In conclusion, free 25(OH)D and bioavailable 25(OH)D are more precise determinants of the vitamin D status than total 25(OH)D in normal pregnancy, whereas total 1,25(OH)2D is superior to free and bioavailable 1,25(OH)2D. Except for PTH, correlations of 25(OH)D and 1,25(OH)2D metabolites with typical clinical chemistry readouts go in opposite directions.
Subject(s)
Biomarkers/blood , Calcitriol/blood , Vitamin D Deficiency/metabolism , Vitamin D/analogs & derivatives , Adult , Bone and Bones/metabolism , Calcium, Dietary/metabolism , Female , Gestational Age , Humans , Kidney/metabolism , Lipid Metabolism/genetics , Lipids/blood , Pregnancy , Pregnant Women , Vitamin D/blood , Vitamin D Deficiency/genetics , Vitamin D-Binding Protein/geneticsABSTRACT
Vitamin D status correct monitoring during pregnancy is critically important for both maternal and fetal health. 25-Hydroxyvitamin D (25(OH)D) - a prohormone of a biologically active 1,25-dihydroxyvitamin D (1,25(OH)2D), despite the lack of biological activity, during the past decades has been routinely used as a main biomarker characterizing vitamin D status. About 85% of 25(OH)D in the bloodstream is bound to its specific carrier - vitamin D-binding protein (DBP), the remaining 15% are loosely bound to albumin, and only less than 0.1% are free in the circulation ("free 25(OH)D"). Total 25(OH)D is the sum of DBP-bound, albumin-bound and free 25(OH)D. According to a "free hormone hypothesis", only free 25(OH)D is able to induce a biological effect. Normal pregnancy is characterized by elevated serum DBP levels, and due to this fact the diagnostic strength of serum total 25(OH)D has been questioned. Free 25(OH)D might be a better characteristic of vitamin D status in this settings. We aimed to compare the diagnostic strength of a routine total 25(OH)D with directly measured free 25(OH)D in normal pregnancy by comparing the association strength between free and total 25(OH)D with biomarkers of bone health (PTH, calcium, bone-specific alkaline phosphatase (BSAP)), lipid metabolism (adiponectin, LDL, HDL), kidney function (urea), endocrine parameters (T4, T3, TSH), and group B water-soluble vitamins. The study was conducted in 368 healthy white pregnant women - residents of north-east Germany. Free 25(OH)D showed an overall better associations with gestational age, markers of bone metabolism (calcium (rho = 0.141, p = 0.007 with free 25(OH)D; rho = 0.060, p = 0.251 with total 25(OH)D) and BSAP (rho = -0.203, p < 0.001 with free 25(OH)D; rho = -0.108, p = 0.038 with total 25(OH)D), lipid metabolism parameters (adiponectin (rho = 0.142, p = 0.008 with free 25(OH)D; rho = 0.054, p = 0.307 with total 25(OH)D), LDL cholesterol (rho = -0.191, p < 0.001 with free 25(OH)D; rho = 0.033, p = 0.539 with total 25(OH)D)) and a kidney function marker (urea (rho = 0.114, p = 0.032 with free 25(OH)D; rho = 0.008, p = 0.887 with total 25(OH)D)) than total 25(OH)D. In conclusion, the current study revealed that free 25(OH)D is a more precise determinant of the vitamin D status during normal human pregnancy than total 25(OH)D. In the settings of normal pregnancy, free 25(OH)D revealed better associations with markers of bone metabolism (calcium, BSAP), lipid metabolism (adiponectin, LDL cholesterol, LDL/HDL ratio) and kidney function (urea) than total 25(OH)D.
Subject(s)
Vitamin D/analogs & derivatives , Vitamins/blood , Adult , Biomarkers/blood , Biomarkers/metabolism , Female , Gestational Age , Humans , Pregnancy , Protein Binding , Vitamin D/blood , Vitamin D/metabolism , Vitamin D-Binding Protein/metabolism , Vitamins/metabolism , Young AdultABSTRACT
The determination of free 25-hydroxyvitamin D (25(OH)D) as compared to the analysis of total 25-hydroxyvitamin D might reflect better the vitamin D status during pregnancy, since vitamin D-binding protein (DBP) concentrations increase throughout pregnancy and the vast majority of 25(OH)D is tightly bound to DBP thus strongly influencing total 25(OH)D. The concentration of the biologically active free 25(OH)D - on the other hand - is much less dependent on the DBP concentrations. The study was conducted in May-June 2016 in 368 Caucasian pregnant healthy women - residents of Northeastern Germany. Free 25(OH)D was either measured directly by commercial ELISA kit or assessed by calculation via total 25(OH)D, DBP, and albumin serum concentrations. Regardless of the detection method, free 25(OH)D lowers in the 3rd trimester comparing to the 1st trimester (by 12% and 21%, pâ¯<â¯0.05 and pâ¯<â¯0.001, for measured and calculated free 25(OH)D, respectively), whereas total 25(OH)D was not decreased in late pregnancy. DBP rises with gestational age. Total 25(OH)D was not correlated with serum calcium (pâ¯=â¯0.251), whereas free 25(OH)D was significantly (pâ¯=â¯0.007 for measured free 25(OH)D and pâ¯<â¯0.001 for calculated free 25(OH)D) positively correlated with calcium. All 25(OH)D isoforms were significantly negatively correlated with bone-specific alkaline phosphatase (BSAP), however the correlation strength was the lowest with total 25(OH)D (rhoâ¯=â¯-0.108, pâ¯=â¯0.038), whereas both measured and calculated free 25(OH)D revealed better associations with BSAP (rhoâ¯=â¯-0.203 and rhoâ¯=â¯-0.211 for measured and calculated free 25(OH)D, respectively, pâ¯<â¯0.001 for both). We established pregnancy trimester-specific reference intervals for free measured and calculated 25(OH)D and DBP. Both measured and calculated free 25(OH)D showed better correlations with parameters of the endocrine vitamin D system (calcium and BSAP). Both ways of measuring free 25(OH)D in pregnant women are suitable as novel laboratory parameter for vitamin D status monitoring during human pregnancy and might replace in the future the routine total 25(OH)D assessment.
