Title
MIB-626, an Oral Formulation of a Microcrystalline Unique Polymorph of Ξ²-Nicotinamide Mononucleotide, Increases Circulating Nicotinamide Adenine Dinucleotide and its Metabolome in Middle-Aged and Older Adults
Background
Precursors of nicotinamide adenine dinucleotide (NAD), such as nicotinamide mononucleotide (NMN) or nicotinamide riboside (NR), have shown promise in extending healthspan and alleviating certain age-related conditions in model organisms. However, early-phase trials investigating NAD precursors have produced inconsistent results, and their pharmacokinetics remain not fully elucidated. Here, we present findings on the pharmacokinetics and pharmacodynamics of MIB-626, a unique polymorph Ξ²NMN formulation in microcrystalline form.
Methods
In this 14-day double-blind, placebo-controlled study, 32 adults aged 55-80, who were overweight or obese, were block-randomized and stratified by sex. Participants received either 1,000 mg of MIB-626 once daily, twice daily, or a placebo. Liquid chromatography-tandem mass spectrometry was utilized to measure NMN, NAD, and the NAD metabolome.
Results
Participant characteristics were comparable across groups, and MIB-626 was well-tolerated, with a similar frequency of adverse events in all groups. On Day 14, blood NMN concentrations in MIB-626-treated groups were significantly higher than in the placebo group, showing a 1.7-fold and 3.7-fold increase above baseline in the 1,000 mg once-daily and twice-daily groups, respectively. MIB-626 treatment exhibited dose-related increases in blood NAD levels. Participants treated with NMN showed higher blood levels of NAD metabolites on Days 8 and 14 compared to baseline. Changes in NMN or NAD levels were not associated with sex, body mass index, or age. Minimal unmodified NMN was excreted in the urine.
Conclusion
Both once-daily and twice-daily regimens of MIB-626 at 1,000 mg were deemed safe and correlated with substantial, dose-dependent increases in blood NAD levels and its metabolome. These foundational data, obtained through the use of pharmaceutical-grade Ξ²NMN, standardized sample collection, and validated liquid chromatography-tandem mass spectrometry assays, should aid in the design of efficacy trials targeting specific disease conditions.