Quantitative Analysis of NAD Synthesis-Breakdown Fluxes.
Level 5 - mechanism / opinion, no new human data
Preclinical in vitro and animal isotope-tracing study with no human data
PubMed 29685734 · doi:10.1016/j.cmet.2018.03.018
What was done
Researchers developed and applied isotope-tracer methods to measure NAD synthesis and consumption fluxes in cell lines and in vivo models. They evaluated the tissue distribution and metabolic fates of precursor pathways (tryptophan, nicotinamide) and tested the pharmacokinetic fate of nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) administered via intravenous versus oral routes.
What was found
In cell culture, NAD was synthesized from nicotinamide and consumed primarily by PARPs and sirtuins. In vivo, tryptophan-derived NAD synthesis occurred selectively in the liver, which subsequently released nicotinamide into circulation. Basal NAD turnover varied markedly across tissues, showing high flux in the small intestine and spleen and low flux in skeletal muscle. Intravenous administration of NR or NMN delivered intact molecules to multiple tissues, whereas oral administration resulted in hepatic metabolism to nicotinamide. The abstract reports no numerical values, rates, or confidence intervals.
Why it matters
This work demonstrates that oral NAD-boosting precursors such as NR and NMN undergo extensive first-pass hepatic breakdown to nicotinamide rather than circulating intact to peripheral tissues, providing a mechanistic framework for evaluating oral supplementation strategies.
Limits
The study is entirely preclinical (in vitro cell lines and animal models) with unknown direct applicability to human NAD metabolism. The abstract does not disclose the animal species, sample sizes, kinetic rate numbers, or variance estimates.
Cited by
- supports Animal experiments show that intravenous nicotinamide riboside achieves greater tissue distribution than oral administration.