Study of Chokeberry to Reduce Cardiovascular Disease Risk in Former Smokers

The Effect of Chokeberry Polyphenols on Biomarkers of Cardiovascular Disease and Antioxidant Defenses in Former Smokers

The purpose of this project is to determine whether chokeberry polyphenols mitigate cardiovascular disease risk in former smokers.

Study Overview

• Status: Completed
• Conditions: Cardiovascular Disease; Oxidative Stress
• Intervention / Treatment: Dietary supplement: Placebo capsule; Dietary supplement: Chokeberry Extract; Dietary supplement: Chokeberry extract capsule, acute

Detailed Description

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
• Enrollment (Actual): 62
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • Storrs, Connecticut, United States, 06269
      • Roy E. Jones Building

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Former smoker (previously smoked ≥3 cigarettes/day for at least 1 year, cessation for at least 6 months
• Healthy male or female between 18-65 y
• Serum clinical ranges no more than mildly elevated (serum cholesterol <240 mg/dL) and serum triglyceride (<150 mg/dL)
• Resting blood pressure <140/90 mm Hg
• Stable body weight (±5 lb) for last 2 months
• BMI ranges within normal and overweight (18.5-39 kg/m2)
• Willing to maintain normal exercise level (<7 h/wk)
• Willing to avoid exercise 24 h prior to blood sampling
• Willing to ingest a dietary chokeberry supplement or placebo (500 mg/d) daily for 12 wks.

Exclusion Criteria:

• Previous diagnoses of CVD, diabetes, or arthritis (except for osteo-arthritis)
• Currently being treated for cancer (i.e., chemotherapy, radiation therapy)
• Women with prescribed estrogen replacement therapy
• Practicing slimming diet
• Practicing vegetarian diet
• Currently taking vitamin or mineral supplements or plant pills
• Alcohol consumption exceeding the definition of moderate drinking (2 drinks/day or a total of 12/week for men or 1 drink/day or a total of 7/week for women)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Color-matched rice powder pill	Dietary supplement: Placebo capsule; Color-matched rice powder pill, 2 x 250 mg/day for 12 weeks
Active Comparator: Chokeberry extract capsule	Dietary supplement: Chokeberry Extract; Consumption of 2 x 250 mg chokeberry extract capsules daily for 12 weeks.
Experimental: Chokeberry extract capsule (acute); Chokeberry extract capsule pharmacokinetics	Dietary supplement: Chokeberry extract capsule, acute; Chokeberry extract capsule, 2 x 250 mg, one-time dose.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline, 6 weeks, 12 weeks of intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	Baseline, 6 weeks, and 12 weeks following intervention
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.	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.	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.	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.	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).	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	Baseline, 12 weeks

Collaborators and Investigators

• Sponsor: University of Connecticut
• Investigators: Principal Investigator: Bradley W Bolling, PhD, University of Connecticut, University of Wisconsin-Madison

Publications and helpful links

General Publications

• Xie L, Lee SG, Vance TM, Wang Y, Kim B, Lee JY, Chun OK, Bolling BW. Bioavailability of anthocyanins and colonic polyphenol metabolites following consumption of aronia berry extract. Food Chem. 2016 Nov 15;211:860-8. doi: 10.1016/j.foodchem.2016.05.122. Epub 2016 May 19.
• Xie L, Vance T, Kim B, Lee SG, Caceres C, Wang Y, Hubert PA, Lee JY, Chun OK, Bolling BW. Aronia berry polyphenol consumption reduces plasma total and low-density lipoprotein cholesterol in former smokers without lowering biomarkers of inflammation and oxidative stress: a randomized controlled trial. Nutr Res. 2017 Jan;37:67-77. doi: 10.1016/j.nutres.2016.12.007. Epub 2016 Dec 10.

Study record dates

Study Major Dates

• Study Start: February 1, 2012
• Primary Completion (Actual): August 1, 2015
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: February 24, 2012
• First Submitted That Met QC Criteria: February 29, 2012
• First Posted (Estimate): March 1, 2012

Study Record Updates

• Last Update Posted (Actual): July 11, 2017
• Last Update Submitted That Met QC Criteria: April 12, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: bioavailability; oxidative stress; polyphenols; LDL cholesterol; aronia
• Additional Relevant MeSH Terms: Cardiovascular Diseases
• Other Study ID Numbers: H11-311; 120068 (Other Identifier: University of Connecticut)