Improving the Understanding of the Response to Vitamin D Supplementation

Vitamin D Deficiency

hypovitaminosis D, vitamin D insufficiency, low vitamin D

It is the investigators hypothesis that the current method of evaluating vitamin D status, measuring circulating 25-hydroxy vitamin D is not providing the full metabolic picture, and is therefore inadequate. The investigators liken this concept to the evolution of cholesterol where initially, total cholesterol was the only measurement, and have since determined the importance of HDL, LDL and triglycerides in evaluating patient status. Similarly, the investigators feel measurement of other vitamin D components such as sulfated vitamin D, circulating vitamin D3 and 3-epi 25-hydroxy vitamin D will offer more comprehensive information about a patient's vitamin D status. It is our overarching hypothesis that a vitamin D assay panel, will enhance understanding of vitamin D status. It is our expectation that the enhanced understanding based on improved measurement capability will ultimately translate to improved definition of vitamin D status and need for supplementation on an individual level.

This hypothesis is supported by several observations. First, recent work finds previously unappreciated vitamin D metabolites, notably 3 epi-25(OH)D348 and sulfated 25(OH)D3, in virtually all human sera and circulating in amounts that vary widely between individuals. These compounds may be measured by current 25(OH)D assays,46, 63 and thereby confound accuracy of such measurements. Secondly, substantial but inadequately understood variability of 25(OH)D response to supplementation and UV exposure exists.15, 42-44 It is likely that currently unappreciated genetic and/or physiologic factors, e.g., differences in absorption or degradation, underpin these observations. Our panel will allow definition of these differences. Finally, the inadequacy of our current approach to classify vitamin D status (singular 25(OH)D measurement) is exemplified by the great between-individual variability in the PTH/25(OH)D relationship as noted above.8, 64 Thus, the investigators believe that exploration of a vitamin D assay panel, consisting of measurements that reflect input (cholecalciferol and ergocalciferol) and confounders to the 25(OH)D assay \[3 epi-25(OH)D and sulfated 25(OH)D\] is essential to accurately define optimal vitamin D status and to determine the ideal approach for vitamin D repletion. To begin testing this hypothesis, the Specific Aims of this research are to document the vitamin D profile response defined as change in serum concentration of: 1. 25(OH)D 2. cholecalciferol 3. 3 epi-25(OH)D 4. Sulfated 25(OH)D following four months of supplementation with 2,200 IU of daily vitamin D3 in postmenopausal women. Our primary outcome variable is the effect of supplementation on serum 25(OH)D3; secondary outcomes are change in cholecalciferol, 3 epi-25(OH)D3 and sulfated 25(OH)D3.

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