Normalized Vitamin D Metabolite Concentrations are Better Correlated to Pharmacological Effects Than Measured Concentrations

Abstract

Background:Vitamin D deficiency has been associated with a multitude of diseases, ranging from fractures to cancer. Nearly 99% of vitamin D metabolites are bound to proteins, altering the relationship between concentration and activity.Methods & results:Normalized concentrations were calculated and validated using published data regarding the correlation of 25-hydroxyvitamin D with bone mineral density. In addition, healthy and kidney disease subjects were recruited for preliminary investigations. Use of the normalizing equations resulted in statistically significant improvements in the relationship between vitamin D metabolites and several markers of health status.Conclusion:Normalized concentrations are similar to clinically reported values and are easier to interpret than free or bioavailable concentrations, since their values match the range of measured total concentrations.

Vitamin D Status and Indices of Mineral Homeostasis in the Population: Differences Between 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D

“…Others have argued that this was a misinterpretation of the concept of vitamin D deficiency and that serum calcidiol <20 ng/mL rarely implies true vitamin D deficiency [1,6]. Additional uncertainties in the definition of vitamin D status are due to the confounding effects of factors such as the variable accuracy of vitamin D assays, the influence of vitamin-D binding protein, and albumin on serum calcidiol levels [7,8,9].…”

The Emerging Role of Nutritional Vitamin D in Secondary Hyperparathyroidism in CKD

“…The sum of DBP-, albumin-bound, and free form of vitamin D is referred to as the total vitamin D. 25D concentration in blood is nearly 1000 times greater than that of 1,25D. DBP has the highest affinity with 25D, but only a 10–100 folds lower affinity to 1,25D because of the steric hindrance of the additional hydroxyl group [96]. Because of relative weak affinity between 25D and albumin, the combination of free and albumin-bound 25D are often referred to as “bioavailable” vitamin D [97].…”

“…VDD is associated with elevated PTH levels and worsening the SHPT. Some studies have reported the high association between free 25D and serum PTH decline [92], bone turnover markers and bone mineral density [96,118], but others who have not reached such conclusions may be due to whether the total or free 25D represents the surrogate marker of vitamin D bioactivity [119,120]. NVD, both the cholecalciferol and calcifediol supplements are effective in increasing the total and free 25D level and are associated with serum PTH level decline [121].…”

Making Sense of Vitamin D Concentrations

“…In the case of vitamin D compounds, the normalized concentration for a particular patient would be the concentration that produces a similar pharmacodynamic effect in an individual with average body composition in which the normal levels of various markers are usually established [15]. The simplest way to normalize concentrations for a particular individual is based on calculating the total concentration that would generate the same free concentration in an individual with average plasma protein binding.…”

“…The simplest way to normalize concentrations for a particular individual is based on calculating the total concentration that would generate the same free concentration in an individual with average plasma protein binding. When normalized concentrations were determined based on measured free or total vitamin D metabolite concentrations, statistically significant improvements in the relationship between vitamin D metabolites and several markers of health status were found [15]. …”