Study of Chokeberry to Reduce Cardiovascular Disease Risk in Former Smokers

Not Applicable

Completed

Conditions: Oxidative Stress
Cardiovascular Disease

Interventions: Dietary Supplement: Chokeberry Extract
Dietary Supplement: Placebo capsule
Dietary Supplement: Chokeberry extract capsule, acute

Registration Number: NCT01541826

Lead Sponsor: University of Connecticut

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 62

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Chokeberry extract capsule	Chokeberry Extract	Chokeberry extract capsule
Color-matched rice powder pill	Placebo capsule	Color-matched rice powder pill
Chokeberry extract capsule (acute)	Chokeberry extract capsule, acute	Chokeberry extract capsule pharmacokinetics

Primary Outcome Measures

Name	Time	Method
LDL Cholesterol	Baseline, 6 weeks, 12 weeks of intervention	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.

Secondary Outcome Measures

Name	Time	Method
Triglycerides	6 and 12 weeks after supplementation	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.
Resting Diastolic Blood Pressure	Baseline, 6 weeks, and 12 weeks following intervention	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.
3-hydroxy-3-methyl-glutaryl Coenzyme A Reductase (HMGR)	Baseline, 12 wk	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.
Adiponectin	Baseline, 6 weeks, 12 weeks	Fasting plasma adiponectin after chronic consumption. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
Interleukin-1 Beta	Baseline, 6 weeks, 12 weeks	Fasting plasma interleukin-1 beta after chronic consumption. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
Energy-adjusted Micronutrient Intake	Baseline, 12 weeks	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.
HDL-cholesterol	6 and 12 weeks after supplementation	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.
Resting Systolic Blood Pressure	Baseline, 6 weeks, and 12 weeks following intervention	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.
LDL Receptor (LDLR)	Change from baseline at 12 weeks	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.
Urinary Excretion of Polyphenols	0 to 24 h after consumption of extract	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.
Intercellular Adhesion Molecule 1	Baseline, 6 weeks, 12 weeks	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.
Glutathione Peroxidase Activity	Baseline, 6 weeks, 12 weeks	Fasting plasma glutathione peroxidase activity after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
Total Cholesterol	6 and 12 weeks after supplementation	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.
LDL Receptor (LDLR) Protein	Baseline, 12 weeks	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.
Tumor Necrosis Factor-alpha	Baseline, 6 weeks, 12 weeks	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.
Soluble Vascular Cell Adhesion Molecule 1	Baseline, 6 weeks, 12 weeks	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.
Superoxide Dismutase Activity	Baseline, 6 weeks, 12 weeks	Fasting plasma superoxide dismutase after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
Energy-adjusted Nutrient Intake: Carbohydrate, Protein, Fat, Fiber	Baseline, 12 weeks	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.
Polyphenol Intake	Baseline, 12 weeks	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.
Intake of Dietary Antioxidant Capacity	Baseline, 12 weeks	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.
Energy-adjusted Vitamin A Intake	Baseline, 12 weeks	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.
Urinary F2-isoprostanes	Baseline and 12 weeks following intervention	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.
Monocyte Chemoattractant Protein-1	Baseline, 6 weeks, 12 weeks	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.
Urinary Polyphenol Excretion	12 weeks	Overnight urinary polyphenol excretion after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
Plasma Area Under the Curve of Chokeberry Polyphenols and Their Metabolites.	0, 0.5, 1, 2, 4, 6, 9, 12, and 24 hours following dose	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).
Interleukin-6	Baseline, 6 weeks, 12 weeks	Fasting plasma interleukin-6 after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
C-reactive Protein	Baseline, 6 weeks, 12 weeks	Fasting plasma C-reactive protein after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
P-selectin	Baseline, 6 weeks, 12 weeks	Fasting plasma P-selectin after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
Total Antioxidant Capacity	Baseline, 6 weeks, 12 weeks	Fasting plasma total antioxidant capacity after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
Catalase Activity	Baseline, 6 weeks, 12 weeks	Catalase activity after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.
Energy Intake	Baseline, 12 weeks	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.