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

McDermott MM, Martens CR, Domanchuk KJ, Zhang D, Peek CB, Criqui MH · Nature Communications

The only randomised human test of an NAD+ precursor combined with resveratrol against a functional endpoint. NR alone improved 6-minute walk distance by 17.6 metres over placebo at 6 months (90% CI +1.8 to infinity, p=0.08 against a prespecified one-sided alpha of 0.10). Adding resveratrol did not: NR plus resveratrol gained 3.7 metres (90% CI -11.2 to infinity, p=0.38). At 3 months both arms beat placebo (22.4 and 20.6 metres). Nausea or vomiting was reported by 36.4% on the combination versus 14.3% on NR alone and 24.1% on placebo, and pill adherence was 52% on the combination versus 75-76% in the other arms.

Population

Adults with lower-extremity peripheral artery disease, mean age 71

Intervention

Nicotinamide riboside 1,000 mg/day, or NR 1,000 mg plus trans-resveratrol 125 mg/day, for 6 months

Comparator

Placebo

Limitations

Ninety participants across three arms; the authors call for confirmation in a larger study. The combination arm's lower adherence and higher nausea confound the comparison — resveratrol's failure to add benefit could reflect either pharmacology or people not taking the pills. NR, not NMN.