It goes without saying that nicotinamide adenine dinucleotide (NAD+) is vital for cellular health and is a key focus within the NADIS community.
While the classical oxidized NAD+ precursors nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) are well characterized, their reduced forms NRH and NMNH have only recently emerged as powerful NAD+ boosters, and their downstream cellular effects beyond NAD⁺ metabolism remain largely unexplored.
In our recent study published in The FASEB Journal, we performed a systematic, side-by-side comparison of NR, NMN, NRH, and NMNH in hepatocytes using a multi-omics approach that combined metabolomics, transcriptomics, and proteomics.
Building on previous work by our NADIS partners, we confirm that the reduced precursors NRH and NMNH are more effective at boosting NAD⁺ than NR and NMN. Interestingly, this increased potency was accompanied by substantially broader effects across the transcriptome, proteome, and metabolome. At both transcript and protein levels, NRH and NMNH upregulated glutathione-S-transferases, indicating activation of cellular stress-related pathways. Notably, this occurred without depletion of glutathione.
Overall, our findings emphasize that NAD⁺ precursors act biologically different. While reduced precursors are more potent NAD⁺ boosters, they also exert broader system-level effects, highlighting the importance of evaluating downstream molecular responses, beyond NAD⁺ levels alone, when considering NAD⁺ precursor strategies for aging and metabolic health.
Reference:
Vinten, K. T. et al. (2026) The FASEB Journal, 40(4), e71582. https://doi.org/10.1096/fj.202501925R