Date of Award

Spring 1-1-2016

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Integrative Physiology

First Advisor

Douglas R. Seals

Second Advisor

Robert S. Mazzeo

Third Advisor

William C. Byrnes

Fourth Advisor

Matthew B. McQueen

Fifth Advisor

Kerrie L. Moreau

Abstract

Cardiovascular diseases (CVD) are the primary cause of death in developed societies. Advancing age is the major risk factor for CVD, with a ~70% prevalence of CVD in adults over 60 years of age. This increase in CVD risk with aging is due primarily to adverse changes to arteries, in particular, the development of two key physiological changes: vascular endothelial dysfunction, characterized by a decline in nitric oxide-mediated endothelium-dependent dilation, and increased stiffness of large elastic arteries. Age-associated arterial dysfunction is driven primarily by the presence of oxidative stress and inflammation.

With the number of adults over the age of 60 expected to double by 2050, preventative and intervention strategies are needed. Curcumin, the active ingredient in the Indian spice turmeric, is a naturally occurring phenol with antioxidant and anti-inflammatory properties. Additionally, 4 weeks of curcumin supplementation improved macrovascular endothelial function and large elastic artery stiffness in older mice.

The goal of this dissertation was to test the hypothesis that curcumin supplementation would improve micro- and macrovascular endothelial function in healthy middle-aged and older adults and these improvements would be associated with increased nitric oxide bioavailability and reduced oxidative stress and inflammation. A secondary hypothesis was curcumin supplementation would improve regional and local large elastic artery stiffness in healthy middle-aged and older adults.

Thirty-nine healthy men and postmenopausal women 45 to 79 years of age were randomized to curcumin (2000 mg/day Longvida) or placebo supplementation for 12 weeks. Curcumin supplementation improved microvascular endothelial function by increasing nitric oxide and reducing vascular oxidative stress, and improved macrovascular endothelial function. In contrast, curcumin had no effect on circulating markers of oxidative stress and inflammation. Secondly, large elastic artery stiffness was assessed in the same individuals before and after 12 weeks of curcumin or placebo supplementation. Curcumin had no influence on regional or local large elastic artery stiffness.

Taken together, these results indicate that curcumin supplementation improves vascular endothelial function, a key antecedent to CVD, and therefore may be a promising prevention for the development of CVD in healthy middle-aged and older adults.

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Physiology Commons

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