Effects of Vitamin D Insufficiency in Man

Vitamin D is a hormone that can either be made in the skin under the influence of sunlight or
absorbed from the diet. Roughly 50% of the U.S. population suffers from an insufficiency of
vitamin D and its more active metabolites. This defect can result in disorders in the bones,
muscles and immune system. In humans, these disorders usually present themselves as decreased
bone mass, decreased muscle strength and increased susceptibility to some infections,
respectively.

Therefore, the purpose of this study is to:

1. determine, by use of skeletal and immune biomarkers in the blood and urine, whether
vitamin D insufficiency exists in differently pigmented ethnic groups; skin pigmentation
blocks vitamin D production in the skin;

2. determine whether the vitamin D status of the host has an impact on bone mass and muscle
function;

3. ascertain whether the vitamin D status of the host has an impact on the function of
cells of the immune system;

4. determine the effects of correction of vitamin insufficiency on the musculoskeletal and
immune systems.

All tests are designed to gauge the state of the circulating and urine factors that
contribute to overall calcium balance and/or imbalance. This will include screening for the
presence or absence of active and latent infection with the agent that causes TB. If evidence
of active TB is identified, one of the physician investigators in this study will inform the
subject of the outcome of the screening test and this information will be reported to the
California State Health Department.

Additionally, blood and related medical information will ultimately be stored in our UCLA
Repository (Human Vitamin D Sample Bank) in the CTRC (Clinical Translational Research Center)
in order to allow sharing of the cells with other approved researchers. The cells may be used
for other future research related to the purposes described above.

We will enroll vitamin D-deficient subjects (African American, Hispanic and white) and
vitamin D-sufficient matching controls against which to compare them. Deficient subjects will
be randomized to receive a total of 500,000 IU of vitamin D2 or D3, at the standard
replacement dose of vitamin 50,000 IU twice weekly for 5 weeks. Subjects will complete
screening medical history, questionnaire, biochemical and DXA (if indicated for low bone
mineral density) screening, and exam of muscle strength and/or back curvature (if indicated).
Blood and urine will be collected to gauge the state of the circulating and urine factors
that contribute to the subjects' overall calcium balance and/or imbalance, and to test for
TB. After 5 weeks of vitamin D treatment, subjects will return for repeat testings. Subjects
who are still vitamin D-deficient will undergo an additional 5-week regimen. Subjects for
whom changes in bone mineral density and/or muscle strength are outcome measures will return
one year later for repeat testing.

Inclusion Criteria:

- 25D levels <30 ng/ml (Vitamin D sufficient) OR <20 ng/ml (Vitamin D deficient)

- At least 18 years of age

Exclusion Criteria:

- Hypercalcemia

- Hyperparathyroidism

- Hyperthyroidism

- Hypercalciuria

- Renal disease

- Intestinal malabsorption any disorder that places the subject at risk for developing
hypercalcemia or hypercalciuria during standard vitamin D replacement therapy owing to
the presence of underlying dysregulated vitamin D metabolism (e.g., sarcoidosis, TB,
etc)