Cardiovascular Health of Older Adults and Resveratrol (CORE)

Age-related declines in left ventricular function and endothelium-dependent vasodilation increase the risk for cardiovascular (CV) disease and premature death in older adults. Structural changes to the arterial wall and cardiac muscle are indicated as a cause and appear to be induced by age-related oxidative stress and inflammation and reduced levels of autophagy, the cellular "house-keeping system". Pre-clinical studies indicate that resveratrol (RSV), a polyphenol present mostly in grapes and red wine, may improve left ventricular cardiac muscle and endothelial vasodilator function. Although, RSV has been shown to induce autophagy and improve CV function in animals, evidence for its effects on the CV system in humans is lacking, and there is a need for clinical trials to better understand the effects of RSV on CV function in humans. Because older adults are most likely to have impairments in the central and peripheral CV systems, they represent an ideal population to test the effects of RSV on CV function. Therefore, the central hypothesis is that RSV supplementation will improve age-related left ventricular cardiac muscle function and arterial vasodilation in older adults (> 65 years). The participants will undergo 90 days of RSV treatment (n=12) (1,000mg/day), or (n=12) (1,500mg/day) or placebo (n=12). Before and after the intervention, investigators will non-invasively investigate left ventricular and arterial vasodilator function. Additionally, investigators will examine cardiac muscle damage and inflammatory biomarkers in blood and autophagy and endothelial function protein levels and in skeletal muscle to better understand molecular mechanisms that may underlie the hypothesized beneficial effects of RSV on cardiovascular health in older adults.

Inclusion criteria

All the criteria are the same as in the parent R01 (IRB201400439). Participants must meet all inclusion criteria listed below in order to participate in this study.

• Ability to understand study procedures and to comply with them for the entire length of the study;
• Age 65 years and older;
• Moderately functioning (i.e. a summary score of 4 - 12 on the Short Physical Performance Battery);
• Body Mass Index (BMI) range: 20-39.9 kg/m2;
• Willingness to undergo all testing procedures.

Exclusion criteria

All candidates meeting any of the exclusion criteria listed below at baseline will be disqualified from study participation.

• Non-English speaking individual.
• Failure to provide informed consent;
• Allergy/sensitivity to grapes or Japanese knotweed;
• Current dietary supplementation of grape seed extract or ginko biloba;
• Consumption of ≥ 8 oz. of red wine/dealcoholized red wine/red or purple grape juice more than once weekly;
• Consumption of any dietary supplements containing resveratrol, quercetin, or P. cuspidatum in the previous 90 days;
• Active treatment for cancer, stroke (< 6 months), peripheral vascular disease, coronary artery disease, myocardial infarction (< 6 months), congestive heart failure (stage III or IV), valvular heart disease, major psychiatric disease, severe anemia (blood levels of Hemoglobin < 8 g/dl), bleeding disorders or other blood disorders, liver or renal disease, diabetes, severe osteoarthritis, blindness or deafness, fracture in upper or lower extremity ( < 6 months), upper or lower extremity amputation, or Parkinson's disease;
• Cognitive impairment (i.e. Mini Mental Status Exam ≤ 23 & Clinical Dementia Rating ≥1);
• History of significant head injury;
• Physical activity (i.e. running, bicycling, etc.) ≥ 150 min/week;
• Excessive alcohol use (> 2 drinks/day) or alcohol abuse (> 5 drinks/day for males, or > 4 drinks/day for females);
• History of substance abuse within the past six months;
• Mood disorder (i.e. Center for Epidemiological Studies - Depression (CES-D) ≥ 16);
• History of tobacco use within the past three years;
• Resting heart rate > 120 bpm at screening visit;
• Systolic blood pressure > 160 mm Hg at screening visit;
• Diastolic blood pressure > 90 mm Hg at screening visit;
• Fasting glucose ≥ 126 mg/dL at screening visit;
• Abnormalities in blood chemistry parameters, defined by blood chemistry marker outside of healthy range) as determined by study physician
• Current use of

• anabolic treatments (e.g. growth hormone or testosterone),
• anticholinesterase inhibitor (e.g. Aricept),
• hormone replacement (e.g. Estrogen),
• anticoagulant therapies (note: aspirin -anti-platelet use (≤ 81mg/day) is permitted) or
• use of anti-inflammatory medications more than 3 times per week.;
• Participation in another non-observational clinical trial, or has received an investigational product within 30 days prior to screening/enrollment;
• Refuse to refrain from CoQ10 or alpha-lipoic acid while enrolled in the study.

Temporary Exclusion Criteria

A person meeting any of the following temporary exclusion criteria at the time of screening would not be enrolled but may be re-screened at a later date. A period of 4 weeks is the minimum amount of time required before re-screening for the following conditions can be done.

• Recent bacterial/viral infection (< 2 weeks);
• Acute febrile illness in past 2 months;
• High blood pressure (i.e. ≥ 140/90 mm Hg but ≤ 160/90) at the screening visit; Major surgery or hip/knee replacement (< 6 months);