Clinical trial NCT04283630: Nitrate and Vitamin C on Vascular Health Oxidative Stress
Official title: The Combined Effect of Dietary Nitrate and Vitamin C on Endothelial Function, Oxidative Stress Biomarkers, and Blood Lipids
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Endothelial Dysfunction
Keywords: Nitrate
Vitamin C
Endothelial function
Nitric Oxide
Lead sponsor: University of Kentucky
Sponsor class: OTHER
First posted: 2020-02-25
Enrollment: 23
Sex: ALL
Minimum age (years): 50
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Crossover double blinded crossover study
Primary purpose: TREATMENT

Brief summary: The objective of this study is to examine whether the co-administration of dietary nitrate combined with vitamin C for 4 weeks in patients at risk for CVD would yield robust effects on endothelial function using blood measures and a non-invasive technique (Peripheral Artery Tonometry) compared to dietary nitrate supplementation alone.

Detailed description: This is a 10 week randomized, cross-over, double-blinded, placebo-controlled study. This study was designed to compare the magnitude changes in RHI (primary outcome), plasma NO metabolites (nitrate and nitrite), and plasma vitamin C, plasma oxidized LDL, and blood (secondary outcome) following treatment with inorganic nitrate and vitamin C placebo (N) and inorganic nitrate combined with vitamin C (NC). Following baseline testing, eligible subjects were randomized to receive either treatment (N) or treatment (NC) for 4 weeks (period1), and participants were then crossed over to the alternate treatment for another 4 weeks (period 2). There was a 2-week washout at crossover.

Eligibility criteria: Inclusion Criteria:

* Age: between 50 and 70 years
* Body mass index (BMI) of 18.5-34.9 kg/m2
* Reactive hyperemia index (RHI) of \< or equal to 2
* High cholesterol levels with LDL concentrations (\>130 mg/dL)
* Not receiving any lipid lowering therapy.
* Non-smokers

Exclusion Criteria:

* Evidence of overt atherosclerotic disease (i.e., documented medical history of coronary artery disease, peripheral artery disease, cardiovascular disease, and stroke).
* Any surgery or medical history that could confound study results, such as a history of bowel resection, rheumatoid arthritis, inflammatory bowel disease, celiac disease, diabetes, uncontrolled hypertension (systolic blood pressure \>160 mm Hg or diastolic blood pressure \>100 mm Hg), controlled hypertension on clonidine medication.
* Participants were ineligible if they had been diagnosed with the following medical conditions such as active cancer, severe anemia (Hb \< 10mg/dL), hepatic or renal disease, heart failure, or finger deformities.
* HIV-positive patients on combination antiretroviral therapy because of potential pharmacokinetic interactions with beetroot juice were excluded.
* Participants were also excluded if they reported taking any form of hormone replacement therapy (estrogens, progesterone, and testosterone), multivitamin supplements that provides \>100% of RDA, or any of the following medications that attenuate nitrate conversion to NO: proton pump inhibitors (PPI) and antibiotics.
* Participants who consumed greater than 6 drinks of alcohol (any form) per week, performed structured resistance or aerobic training for more than 1-hour four times per week, or participated in other clinical intervention within the previous 30 days were excluded from the study.
* Eligible subjects were asked to avoid using the mouthwash before and throughout the study duration. In addition, enrolled participants were advised to consume low- vitamin c diet throughout the study. They were provided at the beginning of the study with a list of high vitamin C foods/fortified foods to avoid during the study.

Primary outcomes:
measure: Change of peripheral endothelial function
timeFrame: Change from baseline endothelial function at 4 weeks of each treatment intervention period
Secondary outcomes:
measure: Change of plasma total nitric oxide (NOx)
timeFrame: Change from baseline plasma NOx at 4 weeks of each treatment intervention period
measure: Change of blood biomarker of oxidative stress
timeFrame: Change from baseline oxLDL at 4 weeks of each treatment intervention period
measure: Change of blood lipids
timeFrame: Change from baseline blood lipids at 4 weeks of each treatment intervention period
Other outcomes:
Locations:
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
Study officials:
References:
citation: Basaqr R, Skleres M, Jayswal R, Thomas DT. The effect of dietary nitrate and vitamin C on endothelial function, oxidative stress and blood lipids in untreated hypercholesterolemic subjects: A randomized double-blind crossover study. Clin Nutr. 2021 Apr;40(4):1851-1860. doi: 10.1016/j.clnu.2020.10.012. Epub 2020 Oct 14.