In the United States, cardiovascular disease causes over one-third of all deaths and vitamin D deficiency is an epidemic. An increasing body of data suggests that low vitamin D status adversely impacts the cardiovascular system. It is our fundamental hypothesis that vitamin D deficiency is a risk factor for cardiovascular disease by causing endothelial dysfunction. Moreover, we hypothesize that vitamin D supplementation will restore endothelial function, thereby reducing cardiovascular disease risk.

This pilot research will be conducted in 64 post-menopausal women participating in an existing study of vitamin D supplementation (32 will receive vitamin D3 2,500 IU daily, the others matching placebo) and will explore the effects of vitamin D on endothelial function and arterial reactivity. Post-menopausal women aged 55-65 years are chosen due to their highest risk for development of a subsequent new cardiovascular disease diagnosis. All study participants will have fasting laboratory and noninvasive vascular ultrasound studies performed at baseline and four months later. The primary outcome measure of this pilot study is change in markers of endothelial function and arterial stiffness with vitamin D3 therapy. If our hypotheses are correct, our long-term goals include investigation of the effect of vitamin D repletion on subclinical atherosclerosis and subsequent cardiovascular events.

Inclusion Criteria:

• Healthy, community-dwelling ambulatory post-menopausal women.
• Able and willing to sign informed consent.
• Ages: 55-65.
• Baseline serum 25OHD concentration > 10 ng/ml and < 60 ng/ml
• Not pregnant
• Willing to avoid use of cod-liver oil and non-study vitamin D supplementation; standard multiple vitamins containing ≤ 400 IU used no more than once daily will be allowed.
• Willing to utilize sunscreen of SPF-15 or higher when sun exposure for more than 15 minutes is expected.
• Willing to fast for 12 hours.

Exclusion Criteria:

• Current hypercalcemia (serum calcium > 10.5 mg/dl) or untreated primary hyperparathyroidism.
• History of nephrolithiasis
• Baseline 24-hour urine calcium > 250 mg
• Known risk factors for hypercalcemia, e.g., malignancy, tuberculosis, sarcoidosis, Paget's disease.
• History of any form of cancer within the past five years with the exception of adequately treated squamous cell or basal cell skin carcinoma.
• Known previous personal history of cardiovascular disease.
• Renal failure; defined as a calculated creatinine clearance (using the Cockroft-Gault approach) of ≤ 25 ml/minute.
• Severe end-organ disease, e.g., cardiovascular, hepatic, hematologic, pulmonary, etc., which might limit the ability to complete this study.
• Treatment with any drug known to interfere with vitamin D metabolism, e.g., phenytoin, phenobarbital.
• Known malabsorption syndromes, e.g., celiac disease, active inflammatory bowel disease, etc.
• Known allergy to chocolate.
• Use of medications known to alter bone turnover including bisphosphonates, estrogen, selective estrogen receptor modulators, parathyroid hormone, testosterone or calcitonin.
• Treatment with 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.