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. Against placebo at 6 months, NR alone improved 6-minute walk distance by 17.6 metres (90% CI +1.8 to infinity, p=0.08 against a prespecified one-sided alpha of 0.10), while NR plus resveratrol gained 3.7 metres (90% CI -11.2 to infinity, p=0.38). The two active arms were not significantly different from each other, and among participants who took at least 75% of their pills they nearly converged — 31.0 metres for NR and 26.9 for the combination — which is why the authors attribute the gap to adherence rather than to resveratrol. At 3 months both arms beat placebo (22.4 and 20.6 metres). The combination was harder to take: diarrhoea in 54.6% against 39.3% on NR alone and 27.6% on placebo, nausea or vomiting in 36.4% against 14.3% and 24.1%, and 75%-or-better pill adherence in 52% against 75% and 76%.

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 trial cannot say whether resveratrol adds anything, because it was not powered to compare the two active arms and the combination arm took barely half its pills. Its primary comparison is also one-sided at an alpha of 0.10, which is a lower bar than the conventional two-sided test. NR, not NMN.