Effect of resveratrol onwalking performance in older people with peripheral artery disease the restore randomized clinical trial

IMPORTANCE Research shows that resveratrol, a sirtuin activator in red wine, improves exercise endurance and skeletal-muscle oxidativemetabolism in animals and may enhance vascular function in humans. Resveratrol supplement sales exceed $30 million annually in the United States, but few data are available regarding its efficacy in humans. OBJECTIVE To determine whether resveratrol, 125mg/d or 500mg/d, improves the 6-minute walk performance in patients with peripheral artery disease (PAD). DESIGN, SETTING, AND PARTICIPANTS This parallel-design, double-blind, randomized clinical trial, called Resveratrol to Improve Outcomes in Older People With PAD (RESTORE), was conducted at Northwestern University. Sixty-six participants 65 years or older with PAD were randomized to receive a daily capsule of resveratrol, 125mg or 500mg, or placebo for 6 months. Participants were randomized using a randomly permuted block method stratified by baseline 6-minute walk test performance. This trial was conducted between January 1 2015, and August 5, 2016, and data analyses were performed according to the intention-to-treat concept. INTERVENTIONS Administration of resveratrol, 125 or 500mg/d, or placebo once daily. MAIN OUTCOMES AND MEASURES The primary outcome measurewas the change in 6-minute walk distance at the 6-month follow-up. One of the secondary outcomes was change in maximal treadmill walking time. Because of the preliminary nature of the trial, the a priori power calculation used a 1-sided test with a significance level of P < .10. RESULTS The 66 participants were predominantly men (45 [68%]), had a mean (SD) age of 74.4 (6.6) years, and had a mean (SD) ankle brachial index of 0.67 (0.18). Sixty-four (97%) completed follow-up. Six-month mean (SE) changes in 6-minute walk distance were 4.6 (8.1) mfor the 125-mg resveratrol group, -12.8 (7.5)mfor the 500-mg resveratrol group, and -12.3 (7.9)mfor the placebo group (P = .07 for the 125-mg resveratrol group vs placebo; P = .96 for the 500-mg resveratrol group vs placebo). Six-month mean (SE) changes in maximal treadmill walking time were 0.5 (2.3) minutes for the 125-mg resveratrol group, -0.6 (2.1) minutes for the 500-mg resveratrol group, and 0.4 (2.1) minutes for the placebo group (P = .18 for the 125-mg resveratrol group vs placebo; P = .12 for the 500-mg resveratrol group vs placebo). CONCLUSIONS AND RELEVANCE The RESTORE trial found no consistent evidence that resveratrol improves walking performance in patients 65 years or older with PAD.