Impact of Vitamin D on 25-hydroxyvitamin D Levels and Physical Function

Vitamin D may have favorable effects on muscle but evidence is mixed. It appears that
subjects with low starting levels of 25-hydroxyvitamin D (25OHD) who receive adequate doses
of vitamin D are the most likely to benefit. Vitamin D supplements are being widely
recommended, however the amount of vitamin D needed to achieve the desired level of
25-hydroxyvitamin D in the circulation varies widely among individuals. In this randomized,
placebo-controlled trial, we will determine whether treating older adults with low starting
25OHD levels for one year with up to 1600 IU per day of vitamin D3 will improve muscle
performance (e.g., lower extremity muscle power) and reduce muscle wasting (defined as
reducing nitrogen excretion). Subjects in the vitamin D group will initially take 800 IU of
vitamin D3 daily. If they have not achieved the desired level of 70 nmol/L after 4 mo, their
dose will be doubled to 1600 IU per day for the remainder of the one-year study. The maximal
dose of vitamin D3 to be taken in this study,1600 IU per day, is lower than the current safe
upper limit of 4,000 IU per day set by the Institute of Medicine. Up to 100 healthy men and
women, age 60 years and older will participate in this study. This investigation should
increase our understanding of the impact of supplemental vitamin D on muscle performance.

Inclusion Criteria:

- Men and postmenopausal women age 60 years and older

- Women must be at least 1 year since last menses.

- Subjects must agree not to take their own vitamin D in amounts >600 IU/day (for ages
51-70 years) or >800 IU/day (for ages 71 - 80 years) or more than 600 mg/day of
supplemental calcium.

- Subjects must agree not to have had more than 30 minutes/day of sun exposure at a
southern latitude (< 34 degrees N) in the 2-month period prior to screening and not to
travel south and be exposed to sunshine in the 3-month period prior to their final
visit.

- They will agree not to use tanning salons during the study.

- Screening serum 25OHD of 20 to 50 nmol/L (8.0 to 20 ng/ml).

Exclusion Criteria:

- Kidney stones - in the last 3 years

- Calculated glomerular filtration rate < 30 ml/min

- Screening fasting spot urinary calcium:creatinine ratio (Ca:Cr) > 0.325 (corresponding
to a 24-hr urine calcium of 350 mg)

- Serum calcium exceeding upper normal limit (reference range 8.3 -10.2 mg/dl)

- Other abnormalities in screening labs, at the discretion of the study physician (PI)

- Sarcoidosis

- Evidence of chronic liver disease, including alcoholism

- Cancer treatment in the last year (except basal cell carcinoma) or terminal illness

- Treatment in the last 6 months with estrogen, raloxifene, calcitonin, or testosterone
(vaginal estrogen use okay)

- High dose thiazide therapy (>37.5 mg).

- Treatment in the last year with teriparatide or denosumab

- Treatment in the lsat 2 years with bisphosphonates

- Oral corticosteroid therapy for over 3 weeks within the last 6 months

- Anticonvulsant therapy

- Physical conditions such as osteoarthritis, rheumatoid arthritis, heart failure or
hemiplegia severe enough to prevent reasonable physical activity.

- Non-English speaking subjects (We can't be confident that non-English speaking
subjects could accurately identify intakes of calcium and vitamin D from non-study
sources and this could increase their risk of toxicity from study drug.

- Other abnormalities in screening labs, at the discretion of the study physician (the
PI)