Improving the Understanding of the Response to Vitamin D Supplementation
Condition: Vitamin D Deficiency
MeSH terms: Vitamin D Deficiency
Study type: Interventional
Phase: Phase 3

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): cholecalciferol; Placebo
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): 2000 IU cholecalciferol gelcaps by mouth daily; matching placebo
Intervention MeSH terms: Cholecalciferol; Vitamin D
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Diagnostic
Keywords: hypovitaminosis D; vitamin D insufficiency; low vitamin D