NAD+ and Circulation: What a Real Trial in Peripheral Artery Disease Found

Written by the Nuvirox Research Team

Short answer: yes, with an important caveat about which kind of circulation problem we're talking about. A well-designed randomized trial found that nicotinamide riboside meaningfully improved walking distance in people with peripheral artery disease — a genuine, measurable circulation outcome. But "circulation" covers a lot of ground, and the trial evidence is specific to arterial blood flow, not venous conditions like varicose veins, which involve a different mechanism entirely.

Two different kinds of circulation problems

When people search "NAD+ and circulation," they're often thinking about two very different things. Arterial circulation problems, like peripheral artery disease (PAD), involve narrowed arteries restricting blood flow to the limbs, usually from atherosclerosis. Venous circulation problems, like varicose veins, involve faulty valves in leg veins that let blood pool rather than flow efficiently back to the heart. The research discussed below is specific to arterial circulation and endothelial function — the tissue lining blood vessels. It does not speak to varicose veins, and no clinical trial has tested NAD+ precursors for that specific condition.

The NICE trial: a real result in peripheral artery disease

In 2024, researchers published results from the NICE randomized clinical trial testing nicotinamide riboside, with and without resveratrol, against placebo in people with peripheral artery disease. The trial's primary outcome was change in 6-minute walk distance — a standard, clinically meaningful test of how far someone can walk in six minutes, which reflects real functional circulation to the legs. The results showed that nicotinamide riboside meaningfully improved 6-minute walk distance compared to placebo. Notably, adding resveratrol on top of NR didn't provide additional benefit over NR alone — a useful finding for anyone assuming "more ingredients equals more effect."

Blood pressure and endothelial function trials

A separate randomized, double-blind trial in midlife and older adults (age 50+) with above-normal systolic blood pressure tested nicotinamide riboside at 1000 mg/day for three months. Blood NAD+ levels rose as expected, and — when all subjects were grouped together — mean systolic and diastolic blood pressure was significantly lowered following NR treatment, alongside improvements in vascular endothelial function measured by brachial artery flow-mediated dilation (a standard test of how well blood vessels dilate in response to increased blood flow). A meta-analysis of NMN trials specifically for blood pressure, however, found the picture less settled overall — animal studies show a clearer benefit than the human trial evidence currently supports, and the authors called the human efficacy data "unclear."

The honest counterweight

Not every circulation-adjacent trial has been positive. A separate 4-week open-label pilot trial in older adults with PAD (a small, uncontrolled study of just 8 participants) reported only "a positive trend" in peripheral endothelial function rather than a statistically confirmed effect — the authors themselves called for larger, controlled trials before drawing firm conclusions. And the NMN blood pressure meta-analysis noted above found human results were "unclear" despite promising animal data. The fair reading across these studies: the strongest, best-controlled evidence (the NICE PAD trial) shows a real functional benefit, but not every smaller or less-controlled study has replicated an equally clean result, and the effect size across different circulation-related outcomes varies.

What NAD+ won't do for circulation

None of this research supports NAD+ precursors as a treatment for varicose veins, blood clots, or advanced peripheral artery disease requiring intervention. PAD itself ranges from mild to severe, and severe cases can require medical or surgical treatment that a supplement cannot substitute for. If you have symptoms of PAD (leg pain when walking that resolves with rest, non-healing wounds on the feet, or cold/numb legs) or symptoms suggestive of a blood clot (sudden leg swelling, warmth, and pain), see a doctor rather than self-treating.

Dose used in the trials

The NICE PAD trial and the blood pressure/endothelial function trial both used nicotinamide riboside at doses around 1000 mg/day, taken over three to six months — meaningfully higher than a typical general-wellness serving and sustained over a longer period than most people try a supplement before judging results. That's worth knowing if you're trying to map trial evidence onto a realistic expectation for a standard daily dose.

Frequently asked questions

Does NAD+ help with varicose veins?

There's no clinical trial evidence for this. Varicose veins are a venous condition involving faulty vein valves, which is mechanistically different from the arterial circulation research discussed here. Compression stockings, leg elevation, and in more significant cases, procedures like sclerotherapy, have real evidence for varicose veins.

How much did walking distance improve in the PAD trial?

The trial reported a meaningful improvement in 6-minute walk distance for the NR group compared to placebo over six months; adding resveratrol didn't improve results further. This was a real, prespecified clinical outcome, not a secondary or exploratory measure.

Is it safe to take NAD+ supplements if I have peripheral artery disease?

Talk with your doctor first, especially if you're on medications for PAD or cardiovascular disease. The trial evidence is encouraging, but PAD management should stay under medical supervision, and a supplement shouldn't replace prescribed treatment.

What are warning signs I shouldn't ignore?

Leg pain that consistently starts with walking and resolves with rest, wounds on the feet that won't heal, or sudden swelling/warmth/pain in one leg all warrant prompt medical evaluation rather than a supplement-first approach.

The bottom line

NAD+ and circulation is one of the better-supported topics in this research area — a real randomized trial in people with peripheral artery disease found nicotinamide riboside meaningfully improved a clinically relevant walking-distance outcome, and separate trials show blood pressure and endothelial function benefits in midlife and older adults. But that evidence is specific to arterial circulation, not varicose veins, and severe circulation issues still need medical evaluation. Related reading: NAD+ and blood pressure and NAD+ and heart health.

References

1. Nicotinamide riboside for peripheral artery disease: the NICE randomized clinical trial. Nat Commun. 2024. DOI: 10.1038/s41467-024-49092-5.
2. Nicotinamide riboside lowers systolic blood pressure and improves vascular endothelial function in midlife/older adults with above-normal systolic blood pressure. Am Physiol Soc. 2025.
3. Effects of nicotinamide mononucleotide supplementation on blood pressure: a systematic review and meta-analysis of randomized controlled trials. PMC13028934.
4. Effects of NAD+ supplementation with oral nicotinamide riboside on vascular health and cognitive function in older adults with peripheral artery disease: pilot 4-week open-label trial. J Nutr Health Aging. 2025.

*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease. This article is for informational purposes only and is not a substitute for professional medical advice.