Sunweavers: Supporting Native American Women's Vitamin D Research

Study Overview
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Brief Summary
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Cardiovascular disease (CVD) and diabetes occur commonly among Native Americans (NA), and are leading causes of death among northern US NAs. Moreover, low vitamin D status occurs commonly in this same population. An increasing amount of evidence indicates a correlation between low vitamin D status and CVD and diabetes by contributing to a heightened pro-inflammatory environment within the endothelial lining of blood vessels leading to atherosclerotic disease, and an impaired sensitivity to insulin leading to diabetes. Our fundamental hypothesis is that low vitamin D status is a risk factor for CVD by causing a proinflammatory milieu, thereby leading to endothelial dysfunction. Additionally, the investigators hypothesize that vitamin D supplementation will reduce inflammation, thereby restoring endothelial function and ultimately reducing CVD risk.

Detailed Description
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Low vitamin D status is endemic due to 21st century lifestyle, which limits sun exposure, and inadequate dietary intake. An increasing body of data relates low vitamin D status to increased risk for non-musculoskeletal morbidities including, most notably, cardiovascular disease (CVD) and type II diabetes mellitus (T2DM). CVD, for which T2DM is a major risk factor, causes over one-third of all deaths in the US. Moreover, American Indians (AI) and Alaskan Natives (AN) are 20% more likely to develop CVD and 2.2 times more likely to develop DM than non-Hispanic whites. In fact, AI of the Great Lakes Region (Bemidji Area) have the third highest DM rate in the nation, an age-adjusted DM mortality rate almost three-fold higher than the all-race mortality, and the highest rates of CVD among AI nationally. In this population, where CVD and DM are two of the top four causes of death, our preliminary work finds low vitamin D status commonplace. As low vitamin D status, CVD and T2DM are epidemic among AI, the investigators hypothesize that low vitamin D is causally related to CVD and T2DM by establishing a pro-inflammatory milieu, which in turn predisposes to CVD and T2DM. As such, vitamin D supplementation should reduce markers of inflammation and thereby ultimately reduce risk for CVD and T2DM. This work will explore this possibility by evaluating the effect of vitamin D status on endothelial function (measured by arterial reactivity), plasma biomarkers of inflammation and glucose homeostasis in 100 postmenopausal AI women. Subjects will receive vitamin D3, either 400 or 2,500 IU, daily for six months. The investigators will define the effects of vitamin D status, and subsequent response to supplementation, on endothelial function, arterial stiffness (flow-mediated vasodilation (FMD) of the brachial artery, and carotid to femoral pulse wave velocity (PWV)), plasma markers of inflammation and glucose homeostasis. All study participants will have fasting laboratory and noninvasive vascular ultrasound studies performed at baseline and following three and six months of study. Plasma concentration of pro-inflammatory cytokines will be measured as secondary outcome variables. Fasting blood glucose, insulin and the adipocytokines leptin and adiponectin, will be measured as exploratory outcomes for potential future studies.

Official Title
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Sunweavers: Supporting Native American Women's Vitamin D Research

Conditions
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Vitamin D Deficiency, Cardiovascular Diseases

Intervention / Treatment
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* Dietary Supplement: Vitamin D3


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ambulatory, community dwelling AI woman Postmenopausal up to age 75 years; for women below age 55, postmenopausal status must be confirmed by documentation of serum FSH>30 IU/L and estradiol < 20 pg/ml unless a bilateral oophorectomy is documented. Exclusion Criteria: Serum 25(OH)D < 10 or > 60 ng/ml. Known CVD (history of MI, coronary artery bypass graft surgery, percutaneous coronary intervention, stroke, transient ischemic attack, peripheral arterial disease with claudication). Uncontrolled thyroid disease (thyroid stimulating hormone level outside of normal range). Change in dose of lipid lowering medications within the preceding six weeks. Mastectomy of the right breast Non-English speaking, illiterate, impaired decision making.

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 2500 IU Vitamin D3<br> | Dietary Supplement: Vitamin D3<br>* The vitamin D3 will be taken daily.<br>|
| Active Comparator: 400 IU Vitamin D3<br> | Dietary Supplement: Vitamin D3<br>* The vitamin D3 will be taken daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in markers of endothelial function | This will be determined by evaluating CRP and lipid panel | Baseline visit, 3 month visit and 6 month visit. | 
| Change in arterial stiffness with vitamin D3 supplementation | Change in arterial stiffness will be evaluated with radial tonometry. | one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma concentration of pro-inflammatory cytokines | This will be evaluated by assessing TNF alpha, IL6, VCAM and ICAM | Baseline visit, 3 month visit, and 6 month visit. |