Clinical trial NCT01541826: Study of Chokeberry to Reduce Cardiovascular Disease Risk in Former Smokers
Official title: The Effect of Chokeberry Polyphenols on Biomarkers of Cardiovascular Disease and Antioxidant Defenses in Former Smokers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cardiovascular Disease
Oxidative Stress
Keywords: aronia
LDL cholesterol
polyphenols
bioavailability
oxidative stress
Lead sponsor: University of Connecticut
Sponsor class: OTHER
First posted: 2012-03-01
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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

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.

Eligibility criteria: 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)

Primary outcomes:
measure: LDL Cholesterol
timeFrame: Baseline, 6 weeks, 12 weeks of intervention
Secondary outcomes:
measure: Total Cholesterol
timeFrame: 6 and 12 weeks after supplementation
measure: HDL-cholesterol
timeFrame: 6 and 12 weeks after supplementation
measure: Triglycerides
timeFrame: 6 and 12 weeks after supplementation
measure: Resting Systolic Blood Pressure
timeFrame: Baseline, 6 weeks, and 12 weeks following intervention
measure: Resting Diastolic Blood Pressure
timeFrame: Baseline, 6 weeks, and 12 weeks following intervention
measure: Urinary F2-isoprostanes
timeFrame: Baseline and 12 weeks following intervention
measure: 3-hydroxy-3-methyl-glutaryl Coenzyme A Reductase (HMGR)
timeFrame: Baseline, 12 wk
measure: LDL Receptor (LDLR)
timeFrame: Change from baseline at 12 weeks
measure: LDL Receptor (LDLR) Protein
timeFrame: Baseline, 12 weeks
measure: Plasma Area Under the Curve of Chokeberry Polyphenols and Their Metabolites.
timeFrame: 0, 0.5, 1, 2, 4, 6, 9, 12, and 24 hours following dose
measure: Urinary Excretion of Polyphenols
timeFrame: 0 to 24 h after consumption of extract
measure: Adiponectin
timeFrame: Baseline, 6 weeks, 12 weeks
measure: Interleukin-1 Beta
timeFrame: Baseline, 6 weeks, 12 weeks
measure: Interleukin-6
timeFrame: Baseline, 6 weeks, 12 weeks
measure: Monocyte Chemoattractant Protein-1
timeFrame: Baseline, 6 weeks, 12 weeks
measure: Tumor Necrosis Factor-alpha
timeFrame: Baseline, 6 weeks, 12 weeks
measure: C-reactive Protein
timeFrame: Baseline, 6 weeks, 12 weeks
measure: Intercellular Adhesion Molecule 1
timeFrame: Baseline, 6 weeks, 12 weeks
measure: Soluble Vascular Cell Adhesion Molecule 1
timeFrame: Baseline, 6 weeks, 12 weeks
measure: P-selectin
timeFrame: Baseline, 6 weeks, 12 weeks
measure: Total Antioxidant Capacity
timeFrame: Baseline, 6 weeks, 12 weeks
measure: Catalase Activity
timeFrame: Baseline, 6 weeks, 12 weeks
measure: Glutathione Peroxidase Activity
timeFrame: Baseline, 6 weeks, 12 weeks
measure: Superoxide Dismutase Activity
timeFrame: Baseline, 6 weeks, 12 weeks
measure: Urinary Polyphenol Excretion
timeFrame: 12 weeks
measure: Energy-adjusted Nutrient Intake: Carbohydrate, Protein, Fat, Fiber
timeFrame: Baseline, 12 weeks
measure: Energy Intake
timeFrame: Baseline, 12 weeks
measure: Energy-adjusted Micronutrient Intake
timeFrame: Baseline, 12 weeks
measure: Polyphenol Intake
timeFrame: Baseline, 12 weeks
measure: Intake of Dietary Antioxidant Capacity
timeFrame: Baseline, 12 weeks
measure: Energy-adjusted Vitamin A Intake
timeFrame: Baseline, 12 weeks
Other outcomes:
Locations:
city: Storrs
country: United States
facility: Roy E. Jones Building
state: Connecticut
Study officials:
affiliation: University of Connecticut, University of Wisconsin-Madison
name: Bradley W Bolling, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.