An Expert Report on Nicotinamide Riboside (DB14933)

1.0 Executive Summary

Nicotinamide riboside (NR) is a pyridine-nucleoside form of vitamin B3 that has emerged as a subject of intense scientific and public interest due to its role as a potent and orally bioavailable precursor to nicotinamide adenine dinucleotide (NAD+).[1]

NAD+ is an indispensable coenzyme central to cellular metabolism, energy production, and the regulation of critical signaling pathways that govern cellular health and longevity. The core mechanism of NR involves its efficient conversion to NAD+ via a unique two-step enzymatic pathway mediated by nicotinamide riboside kinases (NRKs), which bypasses rate-limiting steps in other biosynthetic routes.[1]

By elevating the cellular pool of NAD+, NR provides the necessary substrate for key NAD+-consuming enzymes, most notably the sirtuin (SIRT) family of protein deacetylases and poly(ADP-ribose) polymerases (PARPs). These enzymes are integral to processes such as DNA repair, mitochondrial biogenesis, inflammation modulation, and cellular stress responses.[2] As endogenous

NAD+ levels are known to decline with age, this decline has been implicated in the pathophysiology of numerous age-related conditions, positioning NR as a promising agent for healthy aging interventions.[2]

Clinical investigations have established a strong safety profile for NR, with human studies demonstrating its tolerability at doses up to 2,000-3,000 mg per day with few and mild side effects.[6] Research has explored its therapeutic potential across several domains, yielding promising results in neurodegenerative disorders, as exemplified by the NADPARK study in Parkinson's disease, which showed increased cerebral

NAD+ levels and mild clinical improvement.[8] Evidence also suggests benefits for cardiovascular health, including the potential to lower systolic blood pressure in at-risk populations.[9]