Resveratrol and Cardiovascular Health in the Elderly

Resveratrol is found in the leaves and skin of grapes, in peanuts and in the roots of the plant polygonum cupsidatum. Although used since early years in Indian Ayurvedic and Chinese medicine, it came into prominence in the 1990 s as it was believed to be the major reason for the positive effect of wine on cardiovascular health and the French Paradox. Since then, studies have shown that resveratrol affects a number of key cellular pathways and molecular targets with a wide range of biological effects. Noted among these are its effects on the blood vessels, cancer, blood clotting, blood sugar control, cognition, muscle activity and inflammation. Resveratrol also may produce some of the same effects as decreased food intake, perhaps through its action on a molecule in the body called Sirtuin, which is important because this is one of the only approaches that has consistently demonstrated beneficial effects on the aging process. Resveratrol s action and pharmacology has been extensively studied in test tubes, cells, and animals but is only now being explored fully in people. The animal studies include a recent NIA-conducted study in monkeys that demonstrated a reduction in the stiffness of blood vessel over several weeks. Phase 1 and 2 clinical studies in healthy human volunteers or in patients with type II diabetes mellitus have begun to identify possible roles for resveratrol as a dietary supplement and the compound appears to have no harmful effects at doses up to 5 grams per day. There is also growing interest in pharmacological interventions targeting cardiovascular risk factors such as atherosclerosis and type II diabetes to prevent neurodegenerative diseases such as Alzheimer s disease (AD). We will perform a 12-month trial of resVida (an oral preparation of resveratrol) in 120 randomized overweight/obese people over the age of 50 (40 in each group). This is a Phase 1 and 2 double-blind randomized study. One of two doses of study compound (75mg twice daily or 150mg twice daily) or placebo will be self-administered twice a day for 52 weeks to participants 50 years or older. The primary endpoint will be vascular stiffness (as measured by Pulse Wave Velocity) and the secondary endpoint will be exercise capacity as measured by oxygen utilization (VO2max). Testing will be done on the levels of resveratrol in the blood with different doses of the compound. The study will also include measurements of changes in blood glucose levels, inflammation, and exercise capacity. Targeted, quantitative metabolomics assays in blood will be performed to test whether concentrations of small metabolites previously shown to be associated with arterial stiffness, including free oxysterols, amino acids, acycarnitines and glycerophospholipids are modulated by resveratrol. These studies will provide necessary information for further testing of resVida as a compound that could promote healthy aging.