Author ORCID Identifier

Date Available


Year of Publication


Degree Name

Doctor of Philosophy (PhD)

Document Type

Doctoral Dissertation




Pharmacology and Nutritional Sciences

First Advisor

Dr. D. Travis Thomas


Background: Endothelial dysfunction is associated with a decline in the vasodilator nitric oxide (NO) and presents alongside other cardiovascular risk factors in the early stages of atherosclerosis. Independently, inorganic nitrate and vitamin C supplementation have shown promise in providing some restoration of NO bioavailability, reduced oxidative stress, and improvements in endothelial function. Some preliminary evidence has suggested that vitamin C may augment the reduction of nitrite to further liberate NO and improve cardiovascular health. However, co-supplementation has not been adequately studied. Our objective was to compare the effect of inorganic nitrate in the form of concentrated beetroot juice (CBJ) with and without vitamin C on changes in clinical and blood biomarkers of endothelial dysfunction.

Methods: Older adults between 50-70 years with low-density lipoprotein (LDL) >130 mg/dL and RHI score less than 2 were enrolled in a crossover randomized -double-blinded study. Two 4-week intervention periods were separated by a 2-week washout period. Subjects were assigned randomly to start with either CBJ with 1000 mg of vitamin C (NC) or CBJ with a matched vitamin C placebo (N), then switched to the alternate treatment. Vascular testing was measured by EndoPAT to assess reactive hyperemia index (RHI) before and after each interventional period. Fasting blood samples were also collected for serum lipid parameters, plasma vitamin C, plasma oxidized LDL, and plasma NO metabolites to compare the differences between treatments.

Results: Of the 23 enrolled subjects, 18 completed all study visits (7 male, 11 females; age 53-70 years). No significant differences were observed in RHI change (p > 0.05) between the two treatments. Some subjects showed a greater improvement in RHI after nitrate and vitamin C who entered the study with a lower baseline RHI score than those with mean baseline RHI score > 1.67 (RHI: 1.23 vs 1.75; p = 0.02). Changes in plasma nitrate and nitrite were significantly different between treatments (p < 0.01 and p = 0.03 for nitrate and nitrite, respectively). NC produced a greater reduction in the ratio of oxLDL/NOx (p = 0.02). There were significant differences between treatment groups for LDL cholesterol (p = 0.049), total cholesterol (p = 0.05), and triglycerides (p = 0.03) with lower concentrations observed following the NC intervention. HDL was not influenced by dietary nitrate supplementation individually nor in combination with vitamin C.

Conclusions: Co-supplementation of CBJ and vitamin C was effective at enriching the NO pool and reducing a marker of oxidative stress suggesting a potential to improve endothelial function, and reduce the progression of atherosclerotic disease.

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