Why Not Just Take NAD Directly?

 

NAD is a large molecule that cannot enter cells directly:

 

Increasing evidence indicates that NAD+ cannot enter cells directly through the plasma membrane and that it must be converted into smaller, less charged molecules to enter cells

-- Aging and Disease, December 1, 2021

 

NAD+ cannot be taken up directly by the cell, but its precursors can.

-- Trends in Immunology, February 11, 2022

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Perhaps the only study to examine NAD supplementation by IV Therapy found that the NAD was largely excreted, although some was degraded to precursors and generated NAM:

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"The continuous IV infusion of NAD+ at a rate of 3 μmoles/min resulted in a significant (538%) increase in the urine NAD+ excretion rate…The urine excretion rate of the NAM metabolite meNAM was significantly increased (403%) at the 6h time point..."

-- Frontiers in Aging Neuroscience, September 12, 2019

 

The reason NAD supplements work at all is because a number of extracellular enzymes are able to degrade NAD into smaller pieces that can enter cells:

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Extracellular NAD is degraded by three main classes of ectoenzymes [which can] lead to the formation of [adenosine, NMN, NAM, and NR].

-- Frontiers in Oncology, March 19, 2020

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Therefore, putting NAD directly into your blood stream will likely have a positive effect to the extent that (1) it gets broken down into NAM and your salvage pathway is not down-regulated, or (2) it gets broken down into NR and is absorbed as NR.

 

But it is less expensive and more convenient to just take the NR directly as an oral supplement. Anyone telling you that oral supplements do not get absorbed should instead be telling you that NAD doesn't get absorbed.

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