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Differences in tissue-specific utilization of NAD+ boosters (NAD+ flux study) | Rhonda Patrick

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In 2018 Liu et al. investigated the metabolic fate and distribution of varying doses of nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) administered either by oral gavage or intravenously to animals.

What the study found was that when NR or NMN was orally administered to animals, NAD+ levels increased in a dose-dependent manner in the liver, kidney, muscle, and brain.

However, all of the orally administered NR and NMN was converted to nicotinamide in the liver, so the NAD+ found in other tissues was derived from the salvage pathway and not directly from NR or NMN.

When administered intravenously, NR and NMN did reach the liver, kidney, and muscle tissues, raising NAD+ levels in a dose-dependent manner. In some tissues, NR did so somewhat more successfully.

However, neither NR nor NMN crossed the blood-brain barrier. Brain levels of NAD+ did increase indirectly by way of NAD+ derived from the salvage pathway, which requires conversion to nicotinamide as an intermediary step.

The question of whether NAD+ is derived directly from NR or NMN in certain tissues rather than being salvaged from nicotinamide may, in particular, have implications for whether or not oral administration may be hampered in achieving maximal NAD+ status due to the fact that the process of salvaging NAD+ from nicotinamide is subject to feedback inhibition.

For this reason, the fact that intravenous administration of NMN or NR (particularly NR) is more successful suggests that oral administration may have certain limitations that intravenous does not. However, more human research is needed, possibly with higher doses.

Furthermore, it is notable that improved NAD+ status happened in virtually all tissues tested at all doses (oral and intravenous), despite the often predominant involvement of the salvage pathway.

This clip was taken from our larger episode on NAD+ released January 28, 2020: https://youtu.be/hggLOXhFRxc Study: https://www.cell.com/cell-metabolism/…

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