A breakthrough clinical trial in Japan reveals that nicotinamide riboside (NR), a vitamin B3 derivative, significantly improves symptoms of the rare premature aging disease Werner syndrome.
Patients saw boosted cardiovascular health, reduced skin ulcers, and slower kidney decline—all without serious side effects. This is the first evidence that targeting NAD+ depletion could address WS’s underlying biology.
Werner Syndrome: A Devastating Aging Disorder
Werner syndrome is a rare genetic disorder that speeds up the aging process and brings life-threatening complications. In the first clinical trial of its kind, researchers in Japan teamed up with Niagen Bioscience to test nicotinamide riboside (NR), a form of vitamin B3, in people with the condition.
The results were striking: NR boosted heart and blood-vessel health, shrank stubborn skin ulcers, and slowed the loss of kidney function. For a disease with virtually no treatment options, these improvements hint at real hope.
People with Werner syndrome start showing signs of old age in their twenties. Gray hair, balding, cataracts, diabetes, and other illnesses that usually emerge late in life arrive decades early. Painful skin ulcers often resist healing and can lead to amputations, while heart disease and cancer shorten life expectancy. In Japan, about nine out of every million people are affected, and effective therapies have been frustratingly absent.
NAD+ and Its Role in Aging and Disease
Why might NR work? Earlier research from the Bohr lab revealed that Werner patients have low levels of NAD+, a molecule that powers energy production, DNA repair, and many other cellular tasks. Because giving NAD+ directly to humans does not work, scientists explored NR, a natural precursor that the body can readily convert into NAD+.
Animal studies showed NR extending lifespan and countering age-related decline. Human trials in other groups hinted at benefits against inflammation, metabolic issues, and muscle weakness, but its impact on Werner syndrome was a mystery—until now.
Launching the First NR Clinical Trial for WS
In a recent study, a research team led by Associate Professor Masaya Koshizaka from the Center for Preventive Medical Sciences, Chiba University/Department of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Japan, conducted the world’s first rigorous clinical trial of NR in patients with WS. Their paper, published recently in Aging Cell, was co-authored by University President Koutaro Yokote, Assistant Professor Hisaya Kato, Associate Professor Yoshiro Maezawa, and Assistant Professor Mayumi Shoji, all from Chiba University, along with Affiliate Professor Vilhelm Bohr from the University of Copenhagen, Denmark.
This groundbreaking work involved a randomized, double-blind, placebo-controlled trial to evaluate the safety and effectiveness of NR supplementation. The research team enrolled patients with WS in a crossover design, where participants received either a daily dose of NR or a placebo for 26 weeks, switched treatments for another 26 weeks. Researchers tracked NAD+ blood levels, skin ulcer size, arterial stiffness, and kidney function.
NR’s Benefits: NAD+ Boost, Vascular Health, and Kidney Function
NR supplementation significantly increased NAD+ levels in patient blood compared to placebo. Importantly, NR improved arterial stiffness (a marker of cardiovascular disease risk), reduced the skin ulcer area, and appeared to slow the progression of kidney dysfunction—all without any serious side effects. Moreover, a comprehensive examination of metabolites in blood revealed that NR treatment reduced levels of creatinine and other compounds associated with kidney dysfunction. This suggests that NR may help protect kidney function, addressing another serious complication of WS.
Dr. Yasmeen Nkrumah-Elie, Global Director of Niagen Bioscience’s External Research Program called CERP, commented, “This study represents a significant step forward in understanding how NAD+ restoration with NR may help address the underlying biology of WS. By supporting cardiovascular, skin, and kidney health, NR shows potential to improve the quality of life for patients with this devastating condition. We are proud to support Chiba University’s groundbreaking research as part of our ongoing commitment to advancing NAD+ science for rare and underserved diseases.”
A Unified Theory: NAD+ Depletion and Multi-Organ Aging
The treatment’s multiple benefits across many different organ systems indicate that NAD+ depletion may be a fundamental mechanism in WS that can be targeted therapeutically. “Our findings suggest NR could serve as a valuable treatment option for two major symptoms, arteriosclerosis and skin ulcers, as well as for preventing kidney function decline,” explains Dr. Koshizaka. The results are particularly significant given that untreatable skin ulcers affect well over 70% of patients with WS, often leading to amputation, while cardiovascular disease remains a leading cause of early mortality in this population.
Implications for Future Research and Longevity Science
Though larger studies are needed to extend these findings, this pioneering research offers new hope for patients with WS who have long lacked effective treatment options. Beyond its immediate implications for this rare condition, the study also provides valuable insights into the biology of aging and potential interventions to address age-related decline more broadly.
“We hope our work will accelerate studies on not only WS but also other premature aging disorders and common age-related diseases—ultimately helping to extend health span and improve quality of life in both patients and the broader population,” concludes Dr. Koshizaka.
Reference: “Nicotinamide Riboside Supplementation Benefits in Patients With Werner Syndrome: A Double-Blind Randomized Crossover Placebo-Controlled Trial” by Mayumi Shoji, Hisaya Kato, Masaya Koshizaka, Hiyori Kaneko, Yusuke Baba, Takahiro Ishikawa, Naoya Teramoto, Daisuke Kinoshita, Ayano Yamaguchi, Yukari Maeda, Yosuke Inaba, Yuki Shiko, Yoshihito Ozawa, Vilhelm A. Bohr, Yoshiro Maezawa and Koutaro Yokote, 3 June 2025, Aging Cell.
DOI: 10.1111/acel.70093
This work was supported by JSPS KAKENHI [Grant No. JP21K19437, JP22KK0284, JP23H00417, JP23K14705, and JP24K10525], the MHLW Research on Rare and Intractable Diseases Program [Grant No. JP21FC1016, JP21FC2001, and JP24FC1013], AMED [Grant No. JP21jm0210096, JP22ym0126066, JP23ek0109622, and JP24ek0109713], and NordForsk Foundation [Grant No. 119986].
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