Nicotinamide riboside shows promising trend for walking function in PAD 

Nicotinamide riboside was associated with a trend of improved walking function in patients with peripheral artery disease (PAD) compared with placebo. This effect was not further enhanced by additional treatment with resveratrol.

The phase 2 randomised NICE trial (NCT03743636) assessed the effect of nicotinamide riboside, a B3 vitamin and precursor to nicotinamide adenine dinucleotide (NAD+), on walking function in patients with PAD (n=90). “NAD+ is an essential co-factor and enzyme to increase mitochondrial activity, reduce oxidative stress, and increase nitric oxide to improve blood flow and help people with PAD walk better,” explained Prof. Mary McDermott (Northwestern University, IL, USA) [1]. The participants of NICE were randomised to nicotinamide riboside alone (500 mg twice daily), nicotinamide riboside plus resveratrol (125 mg once daily), or a placebo. “Resveratrol increases SIRT1 affinity for NAD+, whereas nicotinamide riboside increases NAD+ abundance. The combination of these 2 agents may, therefore, have a potent effect on SIRT1 activity,” Prof. McDermott outlined the rationale for combining these 2 drugs. The primary outcome was the change in 6-minute walking distance at 6 months.

At 6 months, the 6-minute walking distance showed a non-significant increase of 7.00 meters in the monotherapy arm (P=0.078 vs placebo), decreased by 6.93 meters in the combination therapy arm (P=0.376 vs placebo) and decreased by 10.58 meters in the placebo arm. In a sensitivity analysis selecting only drug-adherent participants (i.e. ≥75% adherence), both experimental arms were associated with improvements in walking distance compared with placebo. In the monotherapy arm with a mean difference of +35.4 meters (P=0.014), and in the combination therapy arm with a mean difference of +30.2 meters (P=0.028).

In summary, there was a favourable trend for monotherapy, which appeared more favourable in a post-hoc analysis limited to drug-adherent participants with PAD. “However, due to the limited sample size, there is a need to confirm these findings in larger clinical trials,” concluded Prof. McDermott.

“NAD boosters are not yet ready for prime time,” commented Dr Naomi Hamburg (Boston University, MA, USA), discussant of the trial. She emphasised that we need to improve access to supervised and home-based programmes and that patients with PAD should be identified as early as possible.

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   1. McDermott MM, et al. Nicotinamide riboside for peripheral artery disease: the NICE randomised clinical trial. FS07, AHA Scientific Sessions 2023, 11–13 November, Philadelphia, USA.

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Posted on 29 January 202429 January 2024