Effect of Resveratrol on Walking 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 oxidative metabolism 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, 125 mg/d or 500 mg/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, 125 mg or 500 mg, 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 500 mg/d, or placebo once daily.

MAIN OUTCOMES AND MEASURES

The primary outcome measure was 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) m for the 125-mg resveratrol group, -12.8 (7.5) m for the 500-mg resveratrol group, and -12.3 (7.9) m for 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.

TRIAL REGISTRATION

clinicaltrials.gov Identifier: NCT02246660.