NAD+ and Werner Syndrome: What a 2025 Randomized Trial Found

Written by the Nuvirox Research Team

Key Points

  • A 2025 randomized, double-blind, crossover, placebo-controlled trial — the first rigorous human trial of NR in Werner syndrome — found real improvements in arterial stiffness and skin ulcer area.
  • Werner syndrome is a rare, hereditary premature-aging disease in which patients develop age-associated conditions decades early, often leading to death before age 60.
  • This is a rare-disease population; findings here don't necessarily extend to typical age-related changes in the general population.

Short answer: yes, in the one rigorous human trial that exists — a rare-disease population showed measurable improvement in arterial stiffness and skin ulcers with NR supplementation. This is one of the more concretely positive findings in this entire batch, with an important caveat about who it applies to and why that caveat matters before drawing broader conclusions.

What Werner syndrome is

Werner syndrome (WS) is a rare hereditary progeroid (premature-aging) syndrome caused by mutations in the WRN gene. Patients develop numerous age-associated diseases decades earlier than typical, often leading to death by age 60 or younger. Because NAD+ depletion has specifically been reported in WS patients, researchers hypothesized it plays a role in the disease's progression, and that restoring it might help. The WRN gene encodes a protein involved in DNA replication, repair, and telomere maintenance, and its dysfunction is thought to accelerate the kind of cellular damage accumulation that, in the general population, unfolds gradually over a normal lifespan — part of why WS has drawn research interest as a kind of natural model for studying accelerated aging biology more broadly, beyond just the disease itself.

Study snapshot

Trial design Randomized, double-blind, crossover, placebo-controlled
Population Patients diagnosed with Werner syndrome
Dose 1,000 mg NR daily, 26 weeks, then crossover to the other arm for 26 more weeks
Key results Improved arterial stiffness (CAVI); decreased skin ulcer area; trend toward less heel-pad thinning
Notable non-finding Only three patients had ulcers — too small a subgroup for definitive conclusions

What the 2025 trial actually found

Led by researchers at Chiba University in Japan, in collaboration with the University of Copenhagen, this was described as the world's first rigorous clinical trial of NR in WS patients. Participants took 1,000 mg of NR or placebo daily for 26 weeks, then crossed over to the other treatment for another 26 weeks — a design that lets each patient serve as their own control. NR significantly improved arterial stiffness, measured by cardio-ankle vascular index (CAVI), and the researchers reported a decrease in skin ulcer area along with a trend toward less thinning of the heel fat pad. Blood creatinine also decreased significantly, suggesting a possible protective effect on kidney function decline. The researchers noted this pattern of findings — improved vascular stiffness, wound healing, and a kidney function marker — is consistent with WS patients' known tendency toward premature atherosclerosis and vascular complications, meaning the trial's positive results align coherently with the specific ways this disease tends to progress, rather than showing scattered, unrelated improvements.

The honest limitations

Only three patients in the study had skin ulcers to begin with, which the researchers explicitly noted is too small a sample to draw definitive conclusions from — a limitation worth taking seriously rather than glossing over, even though the direction of the finding is encouraging. WS is also an extremely rare disease, meaning trial sizes will always be small by necessity, and results in this specific, genetically distinct population don't automatically extend to general, non-WS age-related changes in the broader population.

What improved in the trial70Arterial stiffness (CAVI)55Skin ulcer area35Heel pad thinning
Illustrative summary of directionally positive findings reported in the trial; magnitudes shown are for illustration, not exact effect sizes.

Why this rare-disease finding is still worth knowing about

Werner syndrome functions, in research terms, as a kind of accelerated-aging model — findings here can sometimes offer early signals relevant to broader aging biology, even though they require separate confirmation in non-WS populations before any general claims can be made. This trial stands out because it's a genuinely completed, positive, randomized human trial with objective endpoints (arterial stiffness measurement, wound area, blood creatinine) — rarer than you might expect in this entire research area. It's worth contrasting this with several other topics in this batch, where the available evidence stops at mouse models or ongoing, unreported trials; Werner syndrome is one of the few conditions here where researchers have already completed the full cycle from hypothesis to a published, peer-reviewed, positive human result.

What this means if you or someone you know has Werner syndrome

Werner syndrome requires specialized, ongoing medical management given its wide-ranging health effects. If you or a family member has been diagnosed with WS, this trial is worth bringing directly to your specialist, since it represents genuinely new, peer-reviewed evidence relevant to your specific condition — a rarer thing to be able to say in this field than this article's overall tone might suggest. For related NAD+ research on general aging biology, see our review of NAD+ and anti-aging and NAD+ and telomeres, both of which explore cellular aging mechanisms in non-WS populations with their own separate evidence bases.

Nuvirox NAD+ Restore bottle

FROM NUVIROX

Because of the caveats above, we'd encourage you to read this as general background rather than a treatment plan. If you're curious about the ingredient at the center of this research, here's what's in ours, alongside clinician-routing guidance for anything beyond everyday support:

  • 500 mg Nicotinamide Riboside Chloride (NR) — one of the two most-researched NAD+ precursors, within the dose range used in published human trials
  • 150 mg trans-resveratrol + 50 mg quercetin — polyphenols studied alongside NAD+ pathways for cellular health support
  • 10 mg fenugreek galactomannans to support absorption
  • Backed by a 60-day money-back guarantee — long enough to actually evaluate it the way the research says you should
See how NAD+ Restore is formulated →

Frequently asked questions

Is Werner syndrome the same as normal aging?

No — it's a rare genetic disease causing accelerated onset of many age-associated conditions, distinct from typical aging, though researchers sometimes use it as a model to study aging biology.

Does this trial mean NAD+ supplements slow aging in general?

No. The trial was conducted specifically in Werner syndrome patients, a genetically distinct rare-disease population. Extending this finding to general age-related change in people without WS would go beyond what the trial actually tested.

What dose was used in the trial?

1,000 mg of nicotinamide riboside daily, taken for 26 weeks before crossing over to the placebo arm (or vice versa) for another 26 weeks.

Were there safety concerns in the trial?

The study reported no serious adverse events during the NR treatment phase, which is a meaningful safety data point for this specific population and duration.

How rare is Werner syndrome?

It's considered an ultra-rare disease, with estimates suggesting only a few thousand diagnosed cases worldwide, though prevalence may be somewhat higher in certain populations, including Japan, where genetic screening has identified more cases relative to population size.

Could findings from Werner syndrome research eventually apply to general aging?

That's part of why researchers study accelerated-aging diseases like WS — but any such extension would require its own separate trials in the general population, since a genetically distinct disease with a single-gene cause doesn't behave identically to typical, multifactorial aging.

The bottom line: this is one of the strongest completed human trials in the entire NAD+ precursor research landscape — genuinely positive, randomized, placebo-controlled — with the important caveat that it was conducted in a rare, genetically distinct disease population that doesn't automatically generalize to everyone else. If you're researching this for a WS diagnosis specifically, that's a meaningfully different and more encouraging position to be in than most of the other topics covered in this batch.

References

  1. Shoji M, Kato H, Koshizaka M, et al. Nicotinamide Riboside Supplementation Benefits in Patients With Werner Syndrome: A Double-Blind Randomized Crossover Placebo-Controlled Trial. Aging Cell. 2025. DOI: 10.1111/acel.70093. PMC12341770.

*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.

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