Niacinamide

The NAD⁺ precursors nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) have shown preventive and therapeutic effects in preclinical models of age‑associated decline. Their pharmacokinetics and metabolic fates differ, depending on tissue distribution and expression of biosynthetic enzymes, nucleotidases, and putative transporters. A comprehensive concept linking NAD⁺ metabolism to mammalian aging control has been proposed. The authors state that the field is now poised to test whether these promising preclinical results can be translated to improve human health, emphasizing the need for further investigation of these intermediates.

Fig. 1 NAD+ intermediates, biosynthetic enzymes, and downstream mediators. (Yoshino J, et al., 2018)

To move beyond static NAD concentration measurements, the authors developed isotope‑tracer flux analysis. In cell lines, NAD was synthesized from nicotinamide and consumed largely by PARPs and sirtuins. In vivo, the liver selectively produced NAD from tryptophan and excreted nicotinamide. NAD flux varied widely across tissues, highest in small intestine and spleen, lowest in skeletal muscle. Intravenous nicotinamide riboside or mononucleotide delivered intact molecules to multiple tissues, but oral administration led to hepatic metabolism to nicotinamide. Flux analysis uncovers previously invisible tissue‑specific NAD dynamics.

Fig. 2 Quantitation of NAD turnover in cell culture. (Liu L, et al., 2018)