How NMN is Absorbed？

NMN has a membrane transporter on the surface of some cells, which can directly transfer NMN into the cell, so there are two ways for NMN to enter the cell:

① Directly enter cells through transporters: In early 2019, a paper in Nature Metabolism confirmed this idea. The article found that there is an NMN-specific transporter in the mouse small intestine, called Slc12a8, which is an amino acid and polyamine transporter. It has high selectivity to NMN and does not transport NaMN which is very similar in structure to NMN.

② It is dephosphorylated to NR by CD73 on the cell membrane surface (through the balanced nucleoside transporter ENTs) and enters the cell. It is then catalyzed into NMN by the NRK enzyme in the cytoplasm and enters the mitochondria for utilization (mitochondria do not have NRK).

NMN administration methods include oral administration, intravenous injection, and sublingual administration.

But no matter what kind of supplement method, the one that can increase NAD+ is a good way. In fact, many experiments have shown that NMN can effectively increase the level of NAD+ in various tissues and organs, and its conversion efficiency of NAD+ is much higher than that of other substrates with high concentrations in blood.

1. After NMN is absorbed by the small intestinal epithelial villi, it may be directly utilized by some target organs through microcirculation.

Evidence 1: There is an NMN transporter Slc12a8 in the intestine, and the Slc12a8 protein will transport NMN directly into the cells with the help of sodium ions, and quickly function for the production of NAD+;

Evidence 2: Some organs can directly use NMN to synthesize NAD+. For example, intravenous NMN can be directly absorbed by the kidneys, and a little directly by the liver; the results of isotope tracing confirm that NMN in the cytoplasm can be utilized by mitochondria, and it does not depend on decomposition at all. into NAM and then into NAD+.

2. Different target organs/cells have different selectivity to NAD+ precursors

Some organs/cells can directly use NMN, while others need to be degraded into other intermediates, such as nicotinamide, and then distributed to specific organs to play a role (direct supplementation of nicotinamide cannot efficiently supplement NAD+, in fact, the elderly The nicotinamide content in the body is actually higher)

Evidence 1: A large dose of 500 mg/kg of NMN is injected into the muscle, which is mainly degraded into NAM and then reused; after oral administration of NMN, it is difficult for some organs to directly absorb it, but the content of NAD+ increases rapidly within 15 minutes.

Evidence 2: Regardless of intravenous or oral administration, NAD+ in the brain is almost always gray or red, indicating that brain NAD+ is synthesized from NAM existing in the brain itself and NAM exchanged by the circulatory system. This result indicates to a certain extent that NMN is difficult to pass through blood-brain barrier. However, the experimental results confirmed that NMN supplementation can indeed alleviate the disease process in mice with Alzheimer's disease.

Tag: NMN

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