Effects of vitamin D binding protein phenotypes and vitamin D supplementation on serum total 25(OH)D and directly measured free 25(OH)D

Objective: To determine the relationship between serum total 25-hydroxyvitamin D (25(OH)D), directly measured free 25(OH)D and calculated free 25(OH)D with regard to vitamin D-binding protein (DBP) phenotypes, sex, BMI, age and season, and their interrelationship to vitamin D supplementation. Design, patients and interventions: A randomized controlled trial with 20 000 IU of vitamin D-3 per week or placebo for 12 months was designed. A total of 472 subjects, 236 in each of the intervention groups, were included in the analyses. Main outcome measures: Baseline serum concentrations and increases in serum total 25(OH)D, directly measured free 25(OH)D, calculated free 25(OH)D and DBP. Results: Serum total 25(OH)D and DBP concentrations were significantly lower in subjects with the phenotype Gc2/Gc2 compared to phenotypes with the Gc1S allele, and lower in males compared to females. When using directly measured free 25(OH)D, the differences related to DBP phenotypes and sexes were clearly diminished. All calculated free 25(OH)D concentrations were overestimated compared to the directly measured free 25(OH)D. Serum parathyroid hormone showed an inverse correlation with all vitamin D parameters analyzed. The increases after 12 months of vitamin D supplementation were not significantly different for any of the vitamin D parameters regardless of DBP phenotype, sex or age. Supplementation with vitamin D did not affect serum DBP. Conclusion: Direct measurements of free 25(OH)D reduce the differences seen in total 25(OH)D between DBP phenotype groups and sexes, probably caused by differences in DBP concentrations. With conditions affecting serum DBP concentrations, direct measurements of free 25(OH)D should be considered.