Understanding the physicochemical properties and degradation kinetics of nicotinamide riboside, a promising vitamin B3nutritional supplement

Nicotinamide riboside (NR), a newly recognised form of vitamin B3 and a precursor to nicotinamide adenine dinucleotide (NAD+), has been demonstrated to show therapeutic potential and the possibility of becoming a drug compound in addition to its proven role in rejuvenating ageing cells in mice. However, current literature is devoid of information relating to the physicochemical characterisation of NR and its respective impact upon formulation and final product processing. Here we report physicochemical properties of NR including pKa, log P, solubility, melting point, degradation mechanics, and kinetics, with a special focus on its stability under thermal and physiologically relevant conditions. A simple and rapid HPLC method confirms a base-catalysed hydrolysis degradation of NRCl to nicotinamide and sugar in simulated gastrointestinal (GI) fluids. Given the antagonising effect of nicotinamide against NR, the presented data have a profound impact on how NRCl should be handled both during formulation and storage to prevent formation and to limit accumulation of nicotinamide. The innovative combinatorial use of 1H NMR and Differential Scanning Calorimetry (DSC) was employed to investigate thermal events during NR melting. NRCl degrades upon melting and in solution undergoes hydrolysis in a buffer and in simulated intestinal environments. The results suggest that a proper and evidence-based formulation of NRCl is vital to enable further investigation and clinical analysis of this promising and novel nutrient. Any formulation would need to promote the stability of NRCl and protect it from hostile environments to prevent the accumulation of a potentially antagonistic degradation product. With the current work, we have filled a niche but vital gap in NR literature and the data presented may prove useful in furthering the understanding, specifically the formulation and processing of NRCl.