Free 1,25-dihydroxyvitamin D levels in serum from normal subjects, pregnant subjects, and subjects with liver disease.

Abstract

Abstract. We measured the free concentration of 1,25-dihydroxyvitamin D (1,25[OHJ2D) using centrifugal ultrafiltration, and the level of vitamin D-binding protein (DBP) in 24 normal subjects, 17 pregnant subjects, and 25 alcoholic subjects with liver disease. Our objective was to determine whether the increase in total 1,25(OH)2D levels in pregnant women and the reduction in total 1,25(OH)2D levels in subjects with liver disease reflected a true difference in free 1,25(OH)2D levels or whether such differences were due solely to the variations in DBP levels (and thus, the amount of 1,25[OH]2D bound) in these groups. In subjects with liver disease the mean total 1,25(OH)2tD concentration (22.6±12.5 pg/ml) and the mean DBP concentration (188±105 fsg/ dl) were nearly half the normal values (41.5±11.5 pg/ ml and 404±124 ,g/dl, respectively, P < 0.001), whereas the mean free 1,25(OH)2D level was similar to normal values (209±91 fg/ml and 174±46 fg/ml, respectively). In contrast, in pregnant subjects the mean total 1,25(OH)2D level (82±21 pg/ml) and mean DBP level (576±128 Ag/dl) were significantly higher than normal (P < 0.001). Although the mean percent free 1,25-(OH)2D level in pregnant subjects was below normal (0.359±0.07% vs. 0.424±0.07%, P < 0.001), the mean free 1,25(OH)2D level was 69% higher than normal (294±98 fg/ml vs. 174±46 fg/ml, P < 0.001). When data from all three groups were combined, there was a linear correlation between total 1,25(OH)2D and DBP levels but not between DBP and percent free 1,25(OH)2D levels; the increased DBP levels in the pregnant subjects were associated with less of an effect on percent free 1,25(OH)2D than were the reduced DBP levels in the subjects with liver disease.Our data suggest that (a) free 1,25(OH)2D levels appear to be well maintained even in subjects with liver disease and reduced DBP levels, (b) free 1,25(OH)2D levels are increased during pregnancy despite the increase in DBP levels, and (c) free 1,25(OH)2D levels cannot be inferred accurately from measurements of total 1,25(OH)2D and DBP levels alone in subjects with various physiologic and pathophysiologic conditions.

Vitamin D-binding protein: one more piece in the puzzle of acromegalic osteopathy?

“…Therefore, it is reasonable to hypothesize that applying direct assays in acromegaly, free vitamin D levels may be even lower than those observed by Altinova et al somewhat corroborating the results of this study. On the other hand, in some conditions, VDBP values may be accompanied by a decrease in its affinity for vitamin D ligands with consequent no change in free vitamin D as measured by a direct assay [26]. If this was the case, the indirect evaluation of free vitamin D may underestimate vitamin D bio-availability, and the acromegaly data presented in this study may not have a relevant clinical role.…”

Vitamin D metabolites in captivity? Should we measure free or total 25(OH)D to assess vitamin D status?

“…The centrifugal ultrafiltration assay by which we measured the free levels of 1,25(OH)2D and (51,56,57). In particular, subjects with liver disease have a higher % free vitamin D metabolite concentration than expected for their DBP concentration, whereas the reverse is true in the sera from pregnant women.…”

“…To determine whether only the free vitamin D metabolite could enter cells we (58) The results of our initial studies (51,56) evaluating the free 25(OH)D and 1,25(OH)2D levels in normal subjects and subjects with liver disease or in the latter stages of pregnancy are shown in table 1 except that the measurements of free 25(OH)D during pregnancy are from a more recent study (57) using the immunoassay for free 25(OH)D that will be discussed later.…”

Vitamin D supplementation during pregnancy: safety considerations in the design and interpretation of clinical trials

“…18,62,63 Because the rise in [1,25(OH)2D] is accompanied by a proportional increase in DBP secondary to elevated estrogen production, its implications for calcium homeostasis or other VDR-dependent processes have not been established. 64 Although there are conflicting findings as to whether or not the bioactive free [1,25(OH)2D] is increased relative to the non-pregnant state, 65,66 there is evidence that the proportion of free 1,25(OH)2D significantly increases in the last month of term pregnancy, 67 a period that correlates with increased transplacental calcium transfer to the fetus. The apparent variation in 1,25(OH)2D metabolism throughout gestation underscores the notion that responsiveness to exogenous vitamin D may be modified by the gestational age at which supplementation occurs.…”