Improving the Understanding of the Response to Vitamin D Supplementation
| Status: | Completed |
|---|---|
| Conditions: | Other Indications, Gastrointestinal |
| Therapuetic Areas: | Gastroenterology, Other |
| Healthy: | No |
| Age Range: | 50 - Any |
| Updated: | 11/8/2014 |
| Start Date: | December 2011 |
| End Date: | December 2014 |
| Contact: | Diane Krueger, BS |
| Email: | dckruege@wisc.edu |
| Phone: | 608-265-6410 |
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.
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.
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.
Inclusion Criteria:
- Healthy, community-dwelling ambulatory postmenopausal White, non-Hispanic women
- Able and willing to sign informed consent
- Baseline serum 25(OH)D concentration of 12-20 ng/mL
- Willing to not alter the amount of their baseline vitamin D supplementation during
the course of this study
- Willing to use sunscreen (SPF ≥15) when sun exposure of > 15 minutes is expected
Exclusion Criteria:
- Presence of any measurable circulating 25(OH)D2 on screening measurement
- Current hypercalcemia (serum calcium > 10.5 mg/dl) or untreated primary
hyperparathyroidism
- History of nephrolithiasis
- Known risk factors for hypercalcemia, e.g., malignancy, tuberculosis, sarcoidosis
- History of any form of cancer within the past five years with the exception of
adequately treated squamous cell or basal cell skin carcinoma
- Renal failure; defined as a calculated creatinine clearance (using the Cockroft-Gault
approach) of ≤ 35 ml/minute
- Severe end-organ disease, e.g., cardiovascular, hepatic, hematologic, pulmonary,
etc., which might limit the ability to complete this study
- Known metabolic bone disease, e.g., Paget's disease, osteomalacia
- Treatment with any drug known to interfere with vitamin D metabolism, e.g.,
phenytoin, phenobarbital
- Treatment with high dose vitamin D (≥ 50,000 IU weekly) or any active metabolites of
vitamin D, e.g., calcitriol, within six months of screening
- Use of tanning beds or salons or unwillingness to utilize sunscreen during periods of
sun exposure of 15 minutes or longer
- Planned trips/vacations likely to be associated with substantial amounts of sun
exposure during the course of the study
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