Influence of cholecalciferol supplementation on changes in total 25OHD, free 25OHD, and free 25OHD % in relation to calcium, bone, and glucose homeostasis in young, infertile men

Background and objective

While all types of vitamin D metabolites are bound to vitamin D binding protein and albumin leaving only a small fraction in its free active form, only serum concentrations of total 25-hydroxy vitamin D (25OHD) are used to determine vitamin D status in clinical practice. This study aimed to describe the association of total 25-hydroxy vitamin D (25OHD), calculated free 25OHD, and free 25OHD% (free 25OHD × 100 %/total 25OHD) with mineral, bone, and metabolic variables and assess the impact of cholecalciferol supplementation.

Research design and methods

Secondary data from a single-center, double-blinded, randomized, placebo-controlled clinical trial (NCT01304927) in 307 infertile men. The treatment group (n = 151) initially received 300,000 IU cholecalciferol as a bolus followed by 1400 IU daily for 150 days and was compared to a placebo group (n = 156).

Results

At baseline men with free 25OHD% > 0.03 % had lower serum triglycerides (mmol/L) (0.8 vs. 1.0; p = 0.002), lower LDL (mmol/L) (2.7 vs. 3.1; p = 0.003), lower fasting blood glucose (mmol/L) (4.9 vs. 5.2; p = 0.012), and lower PTH (pmol/L) (3.8 vs. 4.6; p = 0.015) compared to men with free 25OHD% < 0.02 %. When the study population was stratified according to total 25OHD or free 25OHD, the metabolic markers and bone variables did not show any differences. Cholecalciferol supplementation increased total 25OHD after 150 days compared to placebo and the difference was highest in men with lowest vitamin D status. Cholecalciferol supplementation did not change free 25OHD%.

Conclusion

The free 25OHD% is better associated with metabolic health markers such as serum triglycerides, LDL, and fasting blood glucose, but not bone or calciotrophic markers except parathyroid hormone. The free 25OHD% is not affected by cholecalciferol supplementation.