Patients who used oral vitamin D2 supplements demonstrated acute increases in serum vitamin D binding protein, as well as total 24,25-dihydroxyvitamin D, which appeared to reduce the effects of bioavailable 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, according to findings published in the Journal of the Endocrine Society.
“Vitamin D deficiency has been associated with a number of adverse health outcomes including abnormal bone mineralization, heart disease and premature mortality,” Anders H. Berg, MD, PhD, of the department of pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, and colleagues wrote. “Conversely, hypervitaminosis D has been linked with hypercalcemia, tissue calcinosis and renal injury. In response to variations in exposure … and exogenous supplementation, counter regulatory mechanisms are in place to maintain appropriate concentrations of 1,25-hydroxyvitamin D and its precursor 25-dihydroxyvitamin D. … Given the evidence of multiple mechanisms regulating vitamin D signaling, including the influence of [vitamin D binding protein] on concentrations of bioavailable 25-(OH)D, it is likely that there is reciprocal regulation of blood concentrations of [vitamin D binding protein] after administration of vitamin D supplements, which may be an important feedback mechanism for maintaining appropriate concentrations of 1,25-(OH)D.”
The researchers administered five oral doses (50,000 IU) of ergocalciferol to 30 healthy adults for 2 weeks, measuring serum vitamin D binding protein, bioavailable serum 25-(OH)D concentrations and vitamin D metabolites before and after treatment with vitamin D supplements.
Participants’ mean 25-(OH)D2 increased from 1.4 ng/mL to 45.3 ng/mL (P < .0001), the researchers reported, whereas serum 25-(OH)D3 levels decreased from 26.8 ng/mL to 19.7 ng/mL (P < .0001). However, total 25-(OH)D levels rose from a mean of 28.2 ng/mL to 65 ng/mL (P < .0001). Concentrations of vitamin D binding protein rose by a mean of 39.1% (P < .0001), Berg and colleagues wrote. Total 24,25-dihydroxyvitamin D concentrations increased by a mean of 31.3% (P = .0147).
Bioavailable 25-(OH)D rose by a mean of 104.4%, from 5 ng/mL to 8.7 ng/mL (P < .001), whereas 1,25-dihydroxyvitamin D increased by a mean of 32.3%, from 45.5 ng/mL to 58.1 ng/mL (P = .0006), Berg and colleagues reported. Neither parathyroid hormone nor calcium demonstrated any significant changes.
“Following supplementation with high doses of ergocalciferol (29.7 times the daily recommended supplement of 600 IU) among otherwise healthy subjects, a marked rise in 25-(OH)D2 concentrations and a 152% increase in total 25-(OH)D concentrations were accompanied by a 39% rise in blood levels of [vitamin D binding protein] and a 36% rise in [24,25-dihydroxyvitamin D] levels,” the researchers wrote. “Together, the increases in [vitamin D binding protein] and CYP24A1 activity may serve as regulatory mechanisms meant to actively prevent excessive signaling and vitamin D receptor activation, and maintain minerals and respective hormones in homeostatic balance.” – by Andy Polhamus
Disclosures: The authors report no relevant financial disclosures.