Cardiovascular disease (CVD) is the leading cause of death in the United States. In a large percentage of cases, the risk factors for CVD are modifiable if the responsible patient's phenotype is identified and appropriately treated. In particular, the metabolic syndrome encompasses insulin resistance, central obesity, dyslipidemia and hypertension, which are all major risk factors for CVD. These risk factors also cause underlying vascular abnormalities, i.e. endothelial dysfunction, that leads to progression of CVD. Endothelial function is the balance between vasodilating and vasoconstricting substances produced by the endothelium. Endothelial dysfunction is a common feature of insulin resistance and hypertension. In addition, endothelial dysfunction represents a very early step in the process of atherosclerosis and is associated with increased adverse CVD outcomes.

It has been well established that lifestyle modifications (changes in dietary intake and increase in physical activity) can effectively improve CVD risk factors associated with metabolic syndrome. The success of maintaining these lifestyle changes in humans over the long term is poor. Therefore, strategies to reduce prevalence of metabolic syndrome by pharmacological means have been adopted by practicing physicians. However, because of the widespread use of dietary supplements by the general public, nutritional supplementation that includes use of natural products that effectively modify the components of metabolic syndrome represent an attractive approach.

A diet rich in fruits and vegetables clearly has been shown to have significant health benefits. In particular, increased consumption of blueberries has demonstrated beneficial health effects for CVD and certain components of the metabolic syndrome, such as hypertension, insulin resistance and/or type 2 diabetes. These health benefits from blueberries may be attributable to their phenolic bioactive compounds, such as anthocyanins, which also have antioxidant properties. Although both human and animal studies demonstrated the anti-diabetic effect of blueberries, there is a paucity of data detailing the efficacy of increased blueberry consumption upon CVD risk factor modification in human subjects. Thus, given the concern regarding the ability to significantly increase and maintain an individual's fruit and vegetable consumption long-term, the role of dietary supplementation with bioactive components contained in whole blueberries becomes not only an attractive, but a feasible daily dietary intervention.

Our lab has previously shown that obese, nondiabetic and insulin-resistant human subjects that consumed blueberry powder once a day (in the form of a blueberry smoothie) for 6 weeks improved their insulin sensitivity when compared to their counterparts that consumed a placebo smoothie. Unfortunately, definitive blood pressure measurements were not conducted in this study. The investigators used a single clinic measurement which did not show any blood pressure lowering effects with consuming the blueberry smoothies. An 8-wk preclinical trialin spontaneously hypertensive stroke-prone rats, however, showed that supplementation with blueberry powder lowered systolic blood pressure. Thus, it is plausible that blood pressure lowering effects were not seen in our previous study because the investigators did not evaluate a suitable population (with hypertension) and did not use a more precise technique.

Therefore, based on the positive results in our prior human study with the use of blueberry powder increasing insulin sensitivity and given the relationship of CVD risk factors to insulin resistance, this project's overall objective is to examine the role of dietary supplementation with blueberry powder on CVD risk factors in subjects with metabolic syndrome. In particular, the investigators will evaluate changes in insulin sensitivity with the use of the frequently sampled intravenous glucose tolerance test (FSIVGTT), hypertension with the use of a precise ambulatory blood pressure monitoring system and vascular reactivity as a surrogate marker for underlying endothelial abnormalities. To our knowledge, no research studies have evaluated endothelial function and blueberries in humans. To accomplish our goal, the investigators will conduct a randomized, double-blinded and placebo-controlled clinical study with a fixed amount of blueberry powder in the form of a smoothie. The investigators hypothesize that increased daily consumption of blueberry powder will be effective in increasing insulin sensitivity, decreasing blood pressure, and improving vascular wall function in a population with metabolic syndrome that is at high-risk for CVD.