The Effect of Chokeberry Polyphenols on Biomarkers of Cardiovascular Disease and Antioxidant Defenses in Former Smokers
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 62
- 试验地点
- 2
- 主要终点
- LDL Cholesterol
研究概览
简要总结
The purpose of this project is to determine whether chokeberry polyphenols mitigate cardiovascular disease risk in former smokers.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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)
结局指标
主要结局
LDL Cholesterol
时间窗: 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.
次要结局
- HDL-cholesterol(6 and 12 weeks after supplementation)
- Triglycerides(6 and 12 weeks after supplementation)
- Resting Diastolic Blood Pressure(Baseline, 6 weeks, and 12 weeks following intervention)
- 3-hydroxy-3-methyl-glutaryl Coenzyme A Reductase (HMGR)(Baseline, 12 wk)
- Adiponectin(Baseline, 6 weeks, 12 weeks)
- Interleukin-1 Beta(Baseline, 6 weeks, 12 weeks)
- Energy-adjusted Micronutrient Intake(Baseline, 12 weeks)
- Resting Systolic Blood Pressure(Baseline, 6 weeks, and 12 weeks following intervention)
- Urinary Excretion of Polyphenols(0 to 24 h after consumption of extract)
- LDL Receptor (LDLR)(Change from baseline at 12 weeks)
- Intercellular Adhesion Molecule 1(Baseline, 6 weeks, 12 weeks)
- Glutathione Peroxidase Activity(Baseline, 6 weeks, 12 weeks)
- Total Cholesterol(6 and 12 weeks after supplementation)
- LDL Receptor (LDLR) Protein(Baseline, 12 weeks)
- Tumor Necrosis Factor-alpha(Baseline, 6 weeks, 12 weeks)
- Soluble Vascular Cell Adhesion Molecule 1(Baseline, 6 weeks, 12 weeks)
- Superoxide Dismutase Activity(Baseline, 6 weeks, 12 weeks)
- Energy-adjusted Nutrient Intake: Carbohydrate, Protein, Fat, Fiber(Baseline, 12 weeks)
- Polyphenol Intake(Baseline, 12 weeks)
- Intake of Dietary Antioxidant Capacity(Baseline, 12 weeks)
- Energy-adjusted Vitamin A Intake(Baseline, 12 weeks)
- Urinary F2-isoprostanes(Baseline and 12 weeks following intervention)
- Monocyte Chemoattractant Protein-1(Baseline, 6 weeks, 12 weeks)
- Urinary Polyphenol Excretion(12 weeks)
- 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)
- Interleukin-6(Baseline, 6 weeks, 12 weeks)
- C-reactive Protein(Baseline, 6 weeks, 12 weeks)
- P-selectin(Baseline, 6 weeks, 12 weeks)
- Total Antioxidant Capacity(Baseline, 6 weeks, 12 weeks)
- Catalase Activity(Baseline, 6 weeks, 12 weeks)
- Energy Intake(Baseline, 12 weeks)
研究者
Bradley Bolling
Assistant Professor
University of Connecticut