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

Area of Science:

• Gerontology
• Metabolic Medicine
• Clinical Pharmacology

Background:

• Werner syndrome (WS) is a rare genetic disorder causing premature aging and associated diseases.
• Nicotinamide adenine dinucleotide (NAD+) depletion is implicated in WS pathogenesis.
• NAD+ precursors may offer therapeutic benefits for aging and WS.

Purpose of the Study:

• To evaluate the safety and efficacy of nicotinamide riboside (NR) in patients with Werner syndrome.
• To assess NR's impact on NAD+ levels, age-associated pathologies, and metabolic profiles in WS.

Main Methods:

• A double-blind, randomized, crossover, placebo-controlled trial.
• 26-week administration of NR (1000 mg/day) or placebo, followed by crossover.
• Assessment of safety, NAD+ levels, skin ulcers, sarcopenia, CAVI, ABI, and metabolomics.

Main Results:

• NR treatment was safe with no serious adverse events.
• Significant improvement in cardio-ankle vascular index (CAVI), indicating better arterial stiffness.
• Reduced skin ulcer area and a trend towards decreased heel pad thinning.
• Metabolomic analysis showed a decrease in blood creatinine.

Conclusions:

• Nicotinamide riboside (NR) is safe and potentially beneficial for Werner syndrome patients.
• NR may help prevent atherosclerosis, skin ulcers, and renal dysfunction in WS.
• NR supplementation could be a therapeutic strategy for managing accelerated aging diseases.