Vitamin D-Binding Protein, Bioavailable, and Free 25(OH)D, and Mortality: A Systematic Review and Meta-Analysis

Nutrients. 2022 Sep 20;14(19):3894. doi: 10.3390/nu14193894.

Abstract

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.

Keywords: bioavailable 25(OH)D; free 25(OH)D; meta-analysis; mortality; systematic review; vitamin D-binding protein (VDBP).

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Albumins / metabolism
  • Biomarkers
  • Humans
  • Vitamin D / analogs & derivatives
  • Vitamin D Deficiency* / complications
  • Vitamin D-Binding Protein*

Substances

  • Albumins
  • Biomarkers
  • Vitamin D-Binding Protein
  • Vitamin D
  • 25-hydroxyvitamin D