Breakthrough Human Trial: Vitamin B3 Pill Stops Premature Aging In Werner Syndrome

Werner syndrome is a rare disease that causes the body to age faster than normal, leading to problems such as diabetes, heart disease, cancer and wounds that are difficult to heal. Researchers have studied the use of a supplement called nicotinamide riboside (NR), which helps increase a substance essential for cells called NAD+. The study showed that NR is safe and can improve blood vessel health, aid wound healing and protect the kidneys. These results offer hope for a new way to treat this disease.

Werner syndrome (WS), also called premature aging syndrome, is a rare and devastating inherited disease. It causes the body to age much faster than normal. This is due to mutations in a gene called WRN, which plays an important role in protecting and maintaining the DNA in our cells.

WRN helps DNA replicate correctly, repair itself when damaged and maintain the length of telomeres, the structures that protect the ends of chromosomes. Without this protection, DNA will wear out more quickly, leading to accelerated aging. 

Image shows how aging affects the telomeres on chromosomes inside the cell nucleus.

In Japan, where the disease has been most studied, it is estimated that 9 in every million people have Werner syndrome. People with the disease often develop serious problems such as diabetes, high cholesterol, heart disease, cancer, osteoporosis and muscle atrophy (sarcopenia).

In addition, they have short stature, underweight, thin and hardened skin, painful calluses and wounds on the feet that are difficult to heal. Werner syndrome usually leads to early death, around 50 to 60 years of age, and unfortunately there is no treatment that can stop or reverse the progression of the disease.

The image on the left shows a patient with Werner syndrome at age 15. The image on the right shows the same person at age 48. Credit: Department of Pathology, University of Washington, USA.

A recent focus of research into Werner syndrome has been the role of NAD+ (nicotinamide adenine dinucleotide), a molecule essential for the proper functioning of cells.

NAD+ is involved in important processes such as energy production, DNA repair, and protection against cellular aging. In people with Werner syndrome, NAD+ levels in the body are very low. This is linked to the malfunctioning of mitochondria (the power plants of cells) and the accumulation of DNA damage.

NAD+ is also used in excess during the repair of damaged DNA, which ends up further depleting the cells of this substance. For this reason, scientists have begun to investigate whether it would be possible to replenish NAD+ levels and improve the health of people with Werner syndrome.

Among the ways to increase NAD+, one of the most promising is the administration of nicotinamide riboside (NR), a type of vitamin B3, which the body converts into NAD+. Previous studies in mice and even in humans have shown that NR is safe and can bring several benefits.

In animal models, vitamin B3 helped improve mitochondrial function and even prolonged the life of organisms with accelerated aging. In humans, vitamin B3 has already been tested in elderly people and in patients with diseases such as Parkinson's, lupus, heart failure and fatty liver, showing a reduction in inflammation and improvement in some functions of the body, such as liver and heart function.

In light of these data, researchers conducted a rigorous, placebo-controlled clinical trial to test vitamin B3 in patients with Werner syndrome. The study was conducted in such a way that neither the patients nor the doctors knew who was taking vitamin B3 or the placebo, ensuring more reliable results.

Participants took 1000 mg capsules of vitamin B3 once a day for 26 weeks, and then switched groups (those on vitamin B3 switched to placebo and vice versa).

The primary goal was to see if vitamin B3 was safe. Secondary goals included measuring NAD+ levels, the status of skin ulcers, muscle strength, artery stiffness, and blood tests that show kidney and heart health.

The results were encouraging. No serious side effects were reported, showing that vitamin B3 is safe for people with Werner syndrome. In addition, patients had improvements in artery stiffness (which may reduce the risk of heart disease), a reduction in the area of ​​skin ulcers, and a trend toward improvement in heel bone thickness, which may indicate less bone loss.

Blood tests showed a reduction in creatinine levels, suggesting that vitamin B3 may help protect the kidneys.

Telomeres (yellow) marked on human chromosomes (purple).

These findings suggest that vitamin B3 may offer new hope for delaying complications of Werner syndrome, such as atherosclerosis (hardening of the arteries), skin sores, and weakened kidneys.

While larger studies are needed to confirm these results and better understand the long-term benefits, this work represents an important step forward in the search for treatments that truly make a difference for those living with Werner syndrome.

READ MORE:

Nicotinamide Riboside Supplementation Benefits in Patients With Werner Syndrome: A Double-Blind Randomized Crossover Placebo-Controlled Trial

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 

Aging Cell. 03 June 2025 

https://doi.org/10.1111/acel.70093

Abstract: 

Werner syndrome (WS) is a rare hereditary progeroid syndrome caused by mutations in the WRN gene. Patients frequently develop various age-associated diseases prematurely, often leading to early mortality (≤ 60 years of age). Depletion of nicotinamide adenine dinucleotide (NAD)+ has been reported in patients with WS, suggesting a key role in the pathogenesis of WS. NAD+ supplementation may improve the condition of WS and other accelerated aging diseases. Therefore, we conducted a double-blind, randomized, crossover, placebo-controlled trial in patients with WS to evaluate the safety and efficacy of the NAD+ precursor, nicotinamide riboside (NR). NR (1000 mg) or placebo capsules were self-administered once daily for 26 weeks, followed by a crossover to the opposite arm for another 26 weeks. The primary endpoint was the safety of NR. Secondary endpoints included NAD+ levels in plasma, number, and size of skin ulcers, blood examinations, sarcopenia, heel pad thickness, cardio–ankle vascular index (CAVI), and ankle–brachial index. The exploratory endpoints involved metabolome profiles of plasma. No serious adverse events were observed during NR treatment. Importantly, CAVI improved, the skin ulcer area decreased, and heel pad thinning showed a declining trend. Metabolomic analysis revealed a significant decrease in blood creatinine. NR treatment significantly improved arterial stiffness, as indicated by CAVI, and likely suppressed renal functional decline in patients with WS. Therefore, NR may be beneficial for preventing atherosclerosis, skin ulcers, and kidney dysfunction in patients with WS.