Nicotinamide riboside for peripheral artery disease: the NICE randomized clinical trial

Abstract

People with lower extremity peripheral artery disease (PAD) have increased oxidative stress, impaired mitochondrial activity, and poor walking performance. NAD+ reduces oxidative stress and is an essential cofactor for mitochondrial respiration. Oral nicotinamide riboside (NR) increases bioavailability of NAD+ in humans. Among 90 people with PAD, this randomized double-blind clinical trial assessed whether 6-months of NR, with and without resveratrol, improves 6-min walk distance, compared to placebo, at 6-month follow-up. At 6-month follow-up, compared to placebo, NR significantly improved 6-min walk (+7.0 vs. -10.6 meters, between group difference: +17.6 (90% CI: + 1.8,+∞). Among participants who took at least 75% of study pills, compared to placebo, NR improved 6-min walk by 31.0 meters and NR + resveratrol improved 6-min walk by 26.9 meters. In this work, NR meaningfully improved 6-min walk, and resveratrol did not add benefit to NR alone in PAD. A larger clinical trial to confirm these findings is needed.

Fig. 1. NICE Trial consort diagram.

The figure shows the number of participants randomized to each study group and the number of people completing follow-up testing within each group.

Fig. 2. Mean change in 6-min walk distance by study group assignment.

Figure A depicts the 6-month change in 6-min walk (primary outcome) results for N = 90 participants. Mixed models for repeated measures (MMRM) were used to compare 6-month change in 6-min walk distance between the NR + resveratrol and placebo groups and between the NR alone and placebo groups using baseline, 3-month, and 6-month values for 6-min walk distance, adjusting for age, sex, race, and baseline 6-min walk. The a priori statistical analysis plan defined a one-sided P value of <0.10 to define statistical significance. The circle represents NR alone, the square represents NR + resveratrol, and the triangle represents placebo. Figure B depicts 3-month change in 6-min walk (secondary outcome) for N = 90 participants. Mixed models for repeated measures (MMRM) were used to compare change in 6-min walk distance between the NR + resveratrol and placebo groups and between the NR alone and placebo groups using baseline, 3-month, and 6-month values for 6-min walk distance, adjusting for age, sex, race, and baseline 6-min walk. The a priori statistical analysis plan defined a one-sided P value of <0.10 to define statistical significance. The circle represents NR alone, the square represents NR + resveratrol, and the triangle represents placebo. Figure C depicts 6-month change in 6-min walk among the 60 participants who took at least 75% of study pills. Mixed models for repeated measures (MMRM) were used to compare 6-month change in 6-min walk distance between the NR + resveratrol and placebo groups and between the NR alone and placebo groups using baseline, 3-month, and 6-month values for 6-min walk distance, adjusting for age, sex, race, and baseline 6-min walk. The a priori statistical analysis plan defined a one-sided P value of <0.10 to define statistical significance. The circle represents NR alone, the square represents NR + resveratrol, and the triangle represents placebo.