A groundbreaking clinical trial has demonstrated that nicotinamide riboside (NR), a vitamin B3 derivative, significantly improves cardiovascular health, reduces skin ulcer area, and slows kidney function decline in patients with Werner syndrome, a rare genetic disorder causing premature aging. The study, published in Aging Cell on June 3, 2025, represents the first rigorous clinical investigation of NR in this patient population and offers new therapeutic hope for a condition that currently lacks effective treatment options.
Breakthrough Results in Rare Disease Treatment
The research team, led by Associate Professor Masaya Koshizaka from Chiba University's Center for Preventive Medical Sciences, conducted a randomized, double-blind, placebo-controlled crossover trial involving Werner syndrome patients. Participants received either a daily dose of NR or placebo for 26 weeks, then switched treatments for another 26 weeks, allowing researchers to track multiple health parameters including NAD+ blood levels, skin ulcer size, arterial stiffness, and kidney function.
NR supplementation significantly increased NAD+ levels in patient blood compared to placebo and delivered measurable improvements across multiple organ systems. The treatment improved arterial stiffness, a key marker of cardiovascular disease risk, reduced skin ulcer area, and appeared to slow the progression of kidney dysfunction—all without serious side effects.
Addressing Critical Unmet Medical Need
Werner syndrome affects approximately nine per million people in Japan and causes accelerated aging from patients' twenties onward. Individuals develop gray hair, hair loss, cataracts, diabetes, and other age-related conditions typically seen in elderly populations. The condition also causes severe and untreatable skin ulcers that affect over 70% of patients and often lead to limb amputation, while cardiovascular disease remains a leading cause of early mortality.
Previous research from the Bohr laboratory showed that Werner syndrome patients have decreased levels of nicotinamide adenine dinucleotide (NAD+), a biomolecule crucial for cellular energy production, DNA repair, and metabolic processes. This finding suggested that NAD+ depletion may contribute to disease progression, making NR supplementation a logical therapeutic target since direct NAD+ supplementation isn't feasible in mammals.
Comprehensive Metabolic Benefits
The study's comprehensive examination of blood metabolites revealed that NR treatment reduced levels of creatinine and other compounds associated with kidney dysfunction, suggesting the supplement may help protect kidney function and address another serious complication of Werner syndrome. The treatment's multiple benefits across different organ systems indicate that NAD+ depletion may be a fundamental mechanism in Werner syndrome 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 the high prevalence of untreatable skin ulcers in this patient population and the role of cardiovascular disease in early mortality.
Industry Partnership and Future Implications
The study was conducted in collaboration with Niagen Bioscience, which provided its patented nicotinamide riboside ingredient, Niagen, and placebo materials as 250 mg capsules manufactured in a GMP-compliant facility. Dr. Yasmeen Nkrumah-Elie, Global Director of Niagen Bioscience's External Research Program, commented that "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."
Broader Research Implications
Beyond its immediate implications for Werner syndrome treatment, the research provides valuable insights into aging biology and potential interventions for 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.
While larger studies are needed to extend these findings, this pioneering research offers new hope for Werner syndrome patients who have long lacked effective treatment options and establishes a foundation for investigating NAD+ restoration therapy in other aging-related conditions.
