Distribution and Determinants of Vitamin D-Binding Protein, Total, “Non-Bioavailable”, Bioavailable, and Free 25-Hydroxyvitamin D Concentrations among Older Adults
Abstract:Background: serum 25-hydroxyvitamin D (25(OH)D) (“total 25 OH(D)”) is the most commonly used indicator of vitamin D status. However, 25(OH)D is mostly bound to the vitamin D binding protein (VDBP) or albumin in blood, and it has been suggested that the remaining bioavailable or free 25(OH)D may be more relevant for vitamin D associated health outcomes. We aimed to explore distributions and determinants of VDBP, total, bioavailable, complementary “non-bioavailable”, and free 25(OH)D in a large cohort of older a… Show more
“…Both HIV-positive and negative individuals were included in the study. Details of the social demographic characteristics and clinical factors are found elsewhere 23 , 24 .…”
Section: Resultsmentioning
confidence: 99%
“…2 . Other details of the LL-37 analysis have been reported elsewhere 23 . Figure 2 Comparison of serum LL-37 levels among ATB patients, LTBI individuals, and individuals with no TB infection.…”
The free hormone hypothesis postulates that the estimation of free circulating 25 (OH)D may be a better marker of vitamin D status and is of clinical importance compared to total vitamin D fraction. The unbound fraction is involved in biological activities since it is able to penetrate into the cell. Studies have shown that cathelicidin/LL-37 inhibits the growth of Mycobacterium tuberculosis in a vitamin D-dependent manner and therefore adequate vitamin D is required for its expression. The study aimed to determine the association between serum bioavailable and total vitamin D with LL-37 levels in ATB patients, LTBI, and individuals with no TB infection. This was a cross-sectional study in which bioavailable vitamin D and LL-37 levels were measured using competitive ELISA kits and total vitamin D was measured using electrochemilumiscence and consequently determined their association. The mean (SD) bioavailable vitamin D levels of the study participants were 3.8 ng/mL (2.6) and the median (IQR) of LL-37 levels were 320 ng/mL (160, 550 ng/mL). The mean (SD) of total vitamin D levels was 19.0 ng/mL (8.3) ng/mL. Similar weak correlations were observed between the bioavailable and total vitamin D with LL-37 levels, therefore, deviating from our hypothesis.
“…Both HIV-positive and negative individuals were included in the study. Details of the social demographic characteristics and clinical factors are found elsewhere 23 , 24 .…”
Section: Resultsmentioning
confidence: 99%
“…2 . Other details of the LL-37 analysis have been reported elsewhere 23 . Figure 2 Comparison of serum LL-37 levels among ATB patients, LTBI individuals, and individuals with no TB infection.…”
The free hormone hypothesis postulates that the estimation of free circulating 25 (OH)D may be a better marker of vitamin D status and is of clinical importance compared to total vitamin D fraction. The unbound fraction is involved in biological activities since it is able to penetrate into the cell. Studies have shown that cathelicidin/LL-37 inhibits the growth of Mycobacterium tuberculosis in a vitamin D-dependent manner and therefore adequate vitamin D is required for its expression. The study aimed to determine the association between serum bioavailable and total vitamin D with LL-37 levels in ATB patients, LTBI, and individuals with no TB infection. This was a cross-sectional study in which bioavailable vitamin D and LL-37 levels were measured using competitive ELISA kits and total vitamin D was measured using electrochemilumiscence and consequently determined their association. The mean (SD) bioavailable vitamin D levels of the study participants were 3.8 ng/mL (2.6) and the median (IQR) of LL-37 levels were 320 ng/mL (160, 550 ng/mL). The mean (SD) of total vitamin D levels was 19.0 ng/mL (8.3) ng/mL. Similar weak correlations were observed between the bioavailable and total vitamin D with LL-37 levels, therefore, deviating from our hypothesis.
“…Free 25(OH)D, which freely circulates, and 25(OH)D that is loosely bound to albumin, are known as bioavailable 25(OH)D. These forms of vitamin D may dissociate and perform biological actions more rapidly in dynamically perfused tissues [ 15 ]. However, the concentrations of bioavailable and free 25(OH)D are highly correlated with those of total 25(OH)D [ 23 ], even though they make up less than 15% and 1% of total 25(OH)D. This suggests that total 25(OH)D, which may be more reliably determined by established laboratory methods and whose associations with a broad range of health outcomes have been established by an extensive volume of research, may be an excellent surrogate marker even for bioavailable and free 25(OH)D status. Thus, measurements of bioavailable and free 25(OH)D concentrations may not provide relevant incremental value with respect to mortality prediction compared to total 25(OH)D. Nevertheless, further research based on larger studies is required to enhance the scarce empirical evidence on specific contributions of bioavailable and free 25(OH)D as markers of health relevant vitamin D deficiency.…”
Section: Discussionmentioning
confidence: 99%
“…An interesting finding in the study by Yuan et al [ 14 ] and in our meta-analysis of three studies conducted among cancer patient cohorts is the inverse association between VDBP levels and all-cause mortality among cancer patients which was not observed in the general population cohorts. VDBP levels are strongly genetically determined [ 23 ]. If and to what extent their association with mortality among cancer patients can be confirmed in other cancer cohorts and has clinical relevance should be determined in future research.…”
Introduction: Observational studies reported inverse associations between serum total 25-hydroxyvitamin D (25(OH)D) concentrations and mortality. Evolving evidence indicated, however, that bioavailable or free 25(OH)D may be even better predictors of mortality. We conducted a systematic review and meta-analysis to summarize the epidemiological evidence on associations of vitamin D-binding protein (VDBP), albumin-bound, bioavailable, and free 25(OH)D, with mortality. Methods: We systematically searched PubMed and Web of Science, up to 27 May 2022. Predictors of interest included serum or plasma concentrations of VDBP, albumin-bound, bioavailable, and free 25(OH)D. Assessed health outcomes were all-cause and cause-specific mortality. We included studies reporting associations between these biomarkers and mortality outcomes. We applied random-effects models for meta-analyses to summarize results from studies assessing the same vitamin D biomarkers and mortality outcomes. Results: We identified twelve eligible studies, including ten on VDBP, eight on bioavailable 25(OH)D, and eight on free 25(OH)D. No study reported on albumin-bound 25(OH)D and mortality. In meta-analyses, the highest levels of bioavailable and free 25(OH)D were associated with 37% (hazard ratio (HR): 0.63, 95% confidence interval (CI): 0.46, 0.87), and 29% (HR: 0.71, 95% CI: 0.53, 0.97) decrease in all-cause mortality, respectively, compared with the lowest levels. These estimates were similar to those for total 25(OH)D (HR: 0.67, 95% CI: 0.56, 0.80) observed in the same studies. Higher VDBP levels were associated with lower all-cause mortality in cancer patient cohorts. However, no such association was observed in general population cohorts. Conclusions: Similar inverse associations of total, bioavailable, and free 25(OH)D with mortality suggest that bioavailable and free 25(OH)D do not provide incremental value in predicting mortality.
Background. Epidemiological studies consistently find low concentrations of 25-hydroxyvitamin D (25(OH)D) in blood to be associated with increased mortality, and a recent large-scale Mendelian randomization study strongly supports a causal relationship among individuals with low vitamin D status. Evolving evidence suggested that bioavailable or free 25(OH)D may better predict mortality. We aimed to compare the prognostic values of vitamin D-binding protein (VDBP), total, bioavailable, complementary "nonbioavailable", and free 25(OH)D for total and cause-specific mortality in a large population-based cohort study of older adults from Germany.Methods. Bioavailable, complementary "nonbioavailable", and free 25(OH)D concentrations were calculated among 5899 participants aged 50-75 years, based on serum concentrations of total 25(OH)D, VDBP, and albumin. The cohort was followed with respect to total and cause-specific mortality from recruitment in 2001-2002 up to the end of 2018. Multivariable Cox proportional haz-ards regression models were used to assess the associations between various vitamin D biomarkers and mortality, and further stratified by vitamin D status.Results. During a median follow-up of 17.1 years, 1739 participants died, of whom 575, 584, and 94 died of cardiovascular diseases, cancer, and respiratory diseases, respectively. Very similar inverse associations with total mortality (hazard ratio (HR) per standard deviation decrease: 1.17, 95% confidence interval (CI): 1.11, 1.24 for total 25(OH)D; HR: 1.14, 95% CI: 1.08, 1.21 for bioavailable 25(OH)D; HR: 1.12, 95% CI: 1.06, 1.18 for free 25(OH)D) and cause-specific mortalities were seen for all biomarkers of vitamin D status. The strongest associations were consistently seen for respiratory mortality. These inverse associations were strongest among participants with low vitamin D levels (<50 nmol/L). No significant associations were seen between VDBP and mortality.Conclusions. Total, nonbioavailable, bioavailable, and free 25(OH)D showed very similar inverse associations with total and cause-specific mortality, which were strongest among those with low vitamin D status in this large population-based cohort.
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