The purpose of this project is to determine whether chokeberry polyphenols mitigate cardiovascular disease risk in former smokers.
More than 31% of Connecticut adults are former smokers, which may contribute to the high cardiovascular disease (CVD) risk in this state. Atherosclerosis, a hallmark of CVD, is a progressive life-long process. Chronic cigarette smoking increases atherosclerosis and CVD risk. While smoking cessation may lower CVD risk, former smokers still are at high CVD risk. The mechanisms by which smoking accelerates atherosclerosis formation are not fully understood. This knowledge gap prevents development of informed interventions to reduce CVD risk in former smokers. Previous work suggests smoking increases oxidative stress and leads to elevated CVD risk. Former smokers also have decreased antioxidants and markers of vascular function in the circulation, suggesting that despite cessation, smoking has a lingering adverse effect on CVD protective mechanisms. Chokeberry (Aronia melanocarpa) is a native Connecticut plant rich in polyphenol antioxidants and is a promising intervention for reducing CVD risk in former smokers. Chokeberries have diverse polyphenols such as anthocyanins, proanthocyanidins, resveratrol, quercetin, and chlorogenic acid. Chokeberry consumption improves dyslipidemia, inhibits inflammation, and reduces oxidative stress in humans and animals, all of which could contribute to the prevention of CVD in former smokers. Therefore, our central hypothesis is that dietary chokeberry polyphenols reduce CVD risk in former smokers by improving lipid profiles and inhibiting inflammation and oxidative stress. Our long-term goal is to define the mechanisms by which polyphenol antioxidants mitigate CVD risk. The overall goal of this project is to conduct a randomized placebo-controlled clinical trial to evaluate the cardio-protective effects of dietary chokeberry polyphenols in former smokers. Our objectives are to determine 1) the effect of chokeberry polyphenols on plasma cholesterol and triglyceride levels and on gene expression involved in cholesterol metabolism; 2) the extent to which chokeberry improves antioxidant and vascular function in former smokers; and 3) the association of bioavailability of chokeberry polyphenols to changes in biomarkers of CVD risk. Successful completion of this work will result in improved understanding of the role of dietary berry polyphenols to regulate lipid metabolism, inflammation and oxidative stress. Thus, this study will be an important step to developing dietary recommendations for individuals predisposed to CVD risk, particularly former smokers.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
SINGLE
Enrollment
62
Consumption of 2 x 250 mg chokeberry extract capsules daily for 12 weeks.
Color-matched rice powder pill, 2 x 250 mg/day for 12 weeks
Chokeberry extract capsule, 2 x 250 mg, one-time dose.
Roy E. Jones Building
Storrs, Connecticut, United States
LDL Cholesterol
Change in LDL cholesterol from baseline after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
Time frame: Baseline, 6 weeks, 12 weeks of intervention
Total Cholesterol
Change in fasting total cholesterol from baseline after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
Time frame: 6 and 12 weeks after supplementation
HDL-cholesterol
Change in fasting plasma cholesterol from baseline after chronic supplemenation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
Time frame: 6 and 12 weeks after supplementation
Triglycerides
Change in fasting plasma triglycerides from baseline after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
Time frame: 6 and 12 weeks after supplementation
Resting Systolic Blood Pressure
Change in resting systolic blood pressure after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
Time frame: Baseline, 6 weeks, and 12 weeks following intervention
Resting Diastolic Blood Pressure
Change in resting diastolic blood pressure after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
Time frame: Baseline, 6 weeks, and 12 weeks following intervention
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Urinary F2-isoprostanes
Change in resting urinary F2-isoprostanes after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
Time frame: Baseline and 12 weeks following intervention
3-hydroxy-3-methyl-glutaryl Coenzyme A Reductase (HMGR)
Monocyte messenger ribonucleic acid (mRNA) expression normalized to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
Time frame: Baseline, 12 wk
LDL Receptor (LDLR)
Monocyte LDL receptor mRNA normalized to glyceraldehyde-3-phosphate dehydrogenase after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
Time frame: Change from baseline at 12 weeks
LDL Receptor (LDLR) Protein
Monocyte LDL receptor protein by Western blot, normalized to β-actin after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
Time frame: Baseline, 12 weeks
Plasma Area Under the Curve of Chokeberry Polyphenols and Their Metabolites.
Plasma area under the curve of chokeberry polyphenols and their metabolites. Measurement (time 0) began at study baseline. Not determined in chronic arms (Color-matched Rice Powder Pill or Chokeberry Extract Capsule).
Time frame: 0, 0.5, 1, 2, 4, 6, 9, 12, and 24 hours following dose
Urinary Excretion of Polyphenols
Urinary excretion of polyphenols, from 0 to 24 h after consumption of extract, area under the curve (AUC) in Chokeberry Extract Capsule (acute) arm only.
Time frame: 0 to 24 h after consumption of extract
Adiponectin
Fasting plasma adiponectin after chronic consumption. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
Time frame: Baseline, 6 weeks, 12 weeks
Interleukin-1 Beta
Fasting plasma interleukin-1 beta after chronic consumption. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
Time frame: Baseline, 6 weeks, 12 weeks
Interleukin-6
Fasting plasma interleukin-6 after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
Time frame: Baseline, 6 weeks, 12 weeks
Monocyte Chemoattractant Protein-1
Fasting plasma monocyte chemoattractant protein-1 after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
Time frame: Baseline, 6 weeks, 12 weeks
Tumor Necrosis Factor-alpha
Fasting plasma Tumor necrosis factor-alpha after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
Time frame: Baseline, 6 weeks, 12 weeks
C-reactive Protein
Fasting plasma C-reactive protein after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
Time frame: Baseline, 6 weeks, 12 weeks
Intercellular Adhesion Molecule 1
Fasting plasma intercellular adhesion molecule 1 after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
Time frame: Baseline, 6 weeks, 12 weeks
Soluble Vascular Cell Adhesion Molecule 1
Fasting plasma soluble vascular cell adhesion molecule 1 after chronic consumption. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
Time frame: Baseline, 6 weeks, 12 weeks
P-selectin
Fasting plasma P-selectin after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
Time frame: Baseline, 6 weeks, 12 weeks
Total Antioxidant Capacity
Fasting plasma total antioxidant capacity after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
Time frame: Baseline, 6 weeks, 12 weeks
Catalase Activity
Catalase activity after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
Time frame: Baseline, 6 weeks, 12 weeks
Glutathione Peroxidase Activity
Fasting plasma glutathione peroxidase activity after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
Time frame: Baseline, 6 weeks, 12 weeks
Superoxide Dismutase Activity
Fasting plasma superoxide dismutase after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
Time frame: Baseline, 6 weeks, 12 weeks
Urinary Polyphenol Excretion
Overnight urinary polyphenol excretion after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
Time frame: 12 weeks
Energy-adjusted Nutrient Intake: Carbohydrate, Protein, Fat, Fiber
Energy-adjusted intake based on 3-day dietary recalls, determined by the average of baseline and 12 weeks. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
Time frame: Baseline, 12 weeks
Energy Intake
Energy intake reported from 3-day dietary recalls at baseline and 12 weeks, determined by the average of baseline and 12 weeks. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
Time frame: Baseline, 12 weeks
Energy-adjusted Micronutrient Intake
Energy-adjusted micronutrient intake from 3-day dietary recalls at baseline and 12 weeks. Values reported as the average of baseline and 12 weeks. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
Time frame: Baseline, 12 weeks
Polyphenol Intake
Energy-adjusted polyphenol intake assessed by 3-day dietary recalls at baseline and 12 weeks, values determined by average of baseline and 12 weeks. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
Time frame: Baseline, 12 weeks
Intake of Dietary Antioxidant Capacity
Energy-adjusted intake of dietary antioxidant capacity determined by 3-day dietary recalls at baseline and 12 weeks. Values reported as average of baseline and 12 weeks. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
Time frame: Baseline, 12 weeks
Energy-adjusted Vitamin A Intake
Energy-adjusted vitamin A intake from 3-day dietary recalls at baseline and 12 weeks. Values reported as the average of baseline and 12 weeks. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
Time frame: Baseline, 12 weeks