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Vitamin D-binding protein, total, "nonbioavailable," bioavailable, and free 25-hydroxyvitamin D, and mortality in a large population-based cohort of older adults. 2022

Anna Zhu, and Sabine Kuznia, and Tobias Niedermaier, and Bernd Holleczek, and Ben Schöttker, and Hermann Brenner
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.

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. 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 hazards regression models were used to assess the associations between various vitamin D biomarkers and mortality, and further stratified by vitamin D status. 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. 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.

UI MeSH Term Description Entries
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000368 Aged A person 65 years of age or older. For a person older than 79 years, AGED, 80 AND OVER is available. Elderly
D014807 Vitamin D A vitamin that includes both CHOLECALCIFEROLS and ERGOCALCIFEROLS, which have the common effect of preventing or curing RICKETS in animals. It can also be viewed as a hormone since it can be formed in SKIN by action of ULTRAVIOLET RAYS upon the precursors, 7-dehydrocholesterol and ERGOSTEROL, and acts on VITAMIN D RECEPTORS to regulate CALCIUM in opposition to PARATHYROID HORMONE.
D014808 Vitamin D Deficiency A nutritional condition produced by a deficiency of VITAMIN D in the diet, insufficient production of vitamin D in the skin, inadequate absorption of vitamin D from the diet, or abnormal conversion of vitamin D to its bioactive metabolites. It is manifested clinically as RICKETS in children and OSTEOMALACIA in adults. (From Cecil Textbook of Medicine, 19th ed, p1406) Deficiency, Vitamin D,Deficiencies, Vitamin D,Vitamin D Deficiencies
D014809 Vitamin D-Binding Protein An alpha-globulin found in the plasma of man and other vertebrates. It is apparently synthesized in the liver and carries vitamin D and its metabolites through the circulation and mediates the response of tissue. It is also known as group-specific component (Gc). Gc subtypes are used to determine specific phenotypes and gene frequencies. These data are employed in the classification of population groups, paternity investigations, and in forensic medicine. Group-Specific Component Globulin,Vitamin D-Binding Globulin,25-HCC-Binding Protein,25-Hydroxycholecalciferol-Binding Protein,25-Hydroxyvitamin D-Binding Protein,Calciferol-Binding Protein,Gc Globulin,Transcalciferin,25 HCC Binding Protein,25 Hydroxycholecalciferol Binding Protein,25 Hydroxyvitamin D Binding Protein,Calciferol Binding Protein,Component Globulin, Group-Specific,Globulin, Gc,Globulin, Group-Specific Component,Globulin, Vitamin D-Binding,Group Specific Component Globulin,Vitamin D Binding Globulin,Vitamin D Binding Protein
D015331 Cohort Studies Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics. Birth Cohort Studies,Birth Cohort Study,Closed Cohort Studies,Cohort Analysis,Concurrent Studies,Historical Cohort Studies,Incidence Studies,Analysis, Cohort,Cohort Studies, Closed,Cohort Studies, Historical,Studies, Closed Cohort,Studies, Concurrent,Studies, Historical Cohort,Analyses, Cohort,Closed Cohort Study,Cohort Analyses,Cohort Studies, Birth,Cohort Study,Cohort Study, Birth,Cohort Study, Closed,Cohort Study, Historical,Concurrent Study,Historical Cohort Study,Incidence Study,Studies, Birth Cohort,Studies, Cohort,Studies, Incidence,Study, Birth Cohort,Study, Closed Cohort,Study, Cohort,Study, Concurrent,Study, Historical Cohort,Study, Incidence
D015415 Biomarkers Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, ENVIRONMENTAL EXPOSURE and its effects, disease diagnosis; METABOLIC PROCESSES; SUBSTANCE ABUSE; PREGNANCY; cell line development; EPIDEMIOLOGIC STUDIES; etc. Biochemical Markers,Biological Markers,Biomarker,Clinical Markers,Immunologic Markers,Laboratory Markers,Markers, Biochemical,Markers, Biological,Markers, Clinical,Markers, Immunologic,Markers, Laboratory,Markers, Serum,Markers, Surrogate,Markers, Viral,Serum Markers,Surrogate Markers,Viral Markers,Biochemical Marker,Biologic Marker,Biologic Markers,Clinical Marker,Immune Marker,Immune Markers,Immunologic Marker,Laboratory Marker,Marker, Biochemical,Marker, Biological,Marker, Clinical,Marker, Immunologic,Marker, Laboratory,Marker, Serum,Marker, Surrogate,Serum Marker,Surrogate End Point,Surrogate End Points,Surrogate Endpoint,Surrogate Endpoints,Surrogate Marker,Viral Marker,Biological Marker,End Point, Surrogate,End Points, Surrogate,Endpoint, Surrogate,Endpoints, Surrogate,Marker, Biologic,Marker, Immune,Marker, Viral,Markers, Biologic,Markers, Immune

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