Sunweavers: Supporting Native American Women's Vitamin D Research
Condition: Vitamin D Deficiency; Cardiovascular Diseases
MeSH terms: Cardiovascular Diseases; Vitamin D Deficiency
Study type: Interventional
Phase: Phase 2

Summary: 
      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: 
      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.
    

Intervention name(s): Vitamin D3
Intervention type(s): Dietary Supplement
Intervention description(s): The vitamin D3 will be taken daily.
Intervention MeSH terms: Vitamin D; Cholecalciferol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention